Synergistic Dual-Extract Green Synthesis of Zinc Oxide Nanoparticles Using Coriander Stems and Orange Pith: Structural Characterization and In Vitro Biomedical Relevance  

Synergistic Dual-Extract Green Synthesis of Zinc Oxide Nanoparticles Using Coriander Stems and Orange Pith: Structural Characterization and In Vitro Biomedical Relevance | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Synergistic Dual-Extract Green Synthesis of Zinc Oxide Nanoparticles Using Coriander Stems and Orange Pith: Structural Characterization and In Vitro Biomedical Relevance P NAVEEN, Dr Gopi Mamidi, Dr A Indira Priyadarsini This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8478181/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract A sustainable dual-extract green synthesis of zinc oxide nanoparticles (ZnO NPs) is reported using Coriandrum sativum stem extract and Citrus sinensis pith extract—two underutilized kitchen by-products. Unlike conventional chemical routes and single-extract green syntheses, this synergistic dual-extract approach exploits complementary phytochemicals to achieve enhanced control over nucleation, growth, and stabilization of ZnO nanoparticles. Zinc acetate was employed as the precursor under alkaline conditions, followed by controlled calcination to obtain highly crystalline ZnO NPs. Phenolics and terpenoids from coriander stems facilitated Zn²⁺ reduction, while pectin and flavonoids from orange pith acted as efficient capping and stabilizing agents. Comprehensive characterization confirmed the formation of spherical, monodisperse ZnO NPs with an average size of 24 nm (XRD, TEM) and a sharp UV–Vis absorption peak at 373 nm, corresponding to the wurtzite ZnO phase. FTIR analysis revealed persistent phytochemical functional groups (O–H, C = O, C–O–C), confirming effective surface passivation, while zeta potential measurements (− 28.6 mV) demonstrated excellent colloidal stability. Comparative evaluation with reported green syntheses shows that the present dual-extract system yields smaller and more stable ZnO NPs than single-extract methods. The resulting physicochemical features—uniform size, high surface area, and biocompatible surface chemistry—render these ZnO NPs promising for biomedical applications, particularly anticancer and antidiabetic platforms. This work establishes a reproducible, scalable, and eco-friendly route for high-quality ZnO nanoparticle synthesis with translational potential. Biological sciences/Biochemistry Biological sciences/Biotechnology Physical sciences/Chemistry Physical sciences/Materials science Physical sciences/Nanoscience and technology Zinc oxide nanoparticles dual-extract green synthesis coriander stems orange pith phytochemical synergy colloidal stability Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 1. Introduction Nanotechnology enables precise control over matter at the nanoscale, producing materials with size-dependent optical, electronic, catalytic, and biological properties that differ markedly from their bulk counterparts [ 1 – 3 ]. Among metal oxide nanomaterials, zinc oxide nanoparticles (ZnO NPs) have attracted sustained interest due to their wide bandgap (~ 3.37 eV), strong ultraviolet absorption, defect-mediated photoluminescence, chemical stability, and intrinsic antimicrobial activity [ 4 – 6 ]. These attributes underpin a broad range of applications, including photocatalysis, sensors, protective coatings, drug delivery, wound healing, and nanomedicine [ 7 – 9 ]. Despite their technological promise, the large-scale and biomedical translation of ZnO nanoparticles remains limited by the synthesis routes employed. Conventional methods such as sol–gel processing, hydrothermal synthesis, chemical precipitation, and high-temperature pyrolysis often rely on hazardous reagents, high energy input, and synthetic surfactants, raising concerns regarding environmental sustainability and biological safety [ 10 , 11 ]. In addition, residual chemical contaminants and poorly controlled surface chemistry can compromise biocompatibility and reproducibility, particularly for biomedical and in vitro biological studies. Green synthesis has therefore emerged as a sustainable and biologically compatible alternative for ZnO nanoparticle fabrication. In this approach, plant-derived extracts serve as renewable sources of reducing, stabilizing, and capping agents, with phytochemicals such as polyphenols, flavonoids, terpenoids, organic acids, and polysaccharides mediating nanoparticle formation under mild reaction conditions [ 12 – 14 ]. Beyond reducing environmental burden, green synthesis enables in situ surface functionalization of ZnO nanoparticles with bioactive moieties, enhancing dispersion stability, biocompatibility, and suitability for in vitro cellular evaluations [ 15 ]. However, despite these advantages, plant-mediated ZnO synthesis continues to face two critical challenges: (i) limited control over particle size and morphology, and (ii) inadequate long-term colloidal stability [ 16 , 17 ]. These parameters strongly influence optical response, antimicrobial efficiency, cellular uptake, and biological performance in in vitro systems. Numerous reports based on single-plant extracts describe ZnO nanoparticles with broad size distributions and moderate dispersion stability. For instance, ZnO nanoparticles synthesized using Mangifera indica and Parthenium hysterophorus extracts typically exhibit particle sizes in the range of 25–60 nm with zeta potential values above − 20 mV, indicating a tendency toward aggregation [ 18 – 20 ]. Similarly, ZnO nanoparticles prepared using Ziziphus extracts demonstrate notable antimicrobial activity but suffer from variability in size uniformity and long-term stability during in vitro exposure [ 21 , 22 ]. Recent studies suggest that combining multiple plant extracts may create a synergistic phytochemical environment capable of decoupling nucleation and growth processes, thereby enabling improved size regulation and enhanced colloidal stability [ 23 , 24 ]. In this context, a dual-extract strategy employing coriander ( Coriandrum sativum ) stems and orange ( Citrus sinensis ) pith is proposed. Coriander stems are rich in polyphenols and linalool-based terpenoids that can chelate Zn²⁺ ions and regulate crystal growth [ 25 ], while orange pith—often discarded as an agricultural and kitchen waste—is abundant in pectin, flavonoids, and ascorbic acid, which provide effective polymeric capping and electrostatic stabilization [ 26 , 27 ].We hypothesize that the synergistic interaction between these complementary phytochemicals enables controlled nucleation, restricted particle growth, and durable surface passivation without the use of synthetic stabilizers. Accordingly, the objectives of the present study are: (i) to develop a reproducible, low-hazard dual-extract green synthesis route for ZnO nanoparticles, (ii) to systematically characterize their structural, morphological, optical, and colloidal properties, and (iii) to experimentally validate their biological activity through in vitro assays, while benchmarking performance against reported single-extract ZnO systems. By explicitly correlating phytochemical synergy with nanoparticle formation, stability, and in vitro biological response, this work advances green nanotechnology toward reproducible, scalable, and application-ready ZnO nanoparticles. 2. Materials and Methods 2.1. Materials All chemicals used in this study were of analytical grade and employed without further purification. Zinc acetate dihydrate (Zn(CH₃COO)₂·2H₂O, ≥ 99%, Sigma-Aldrich) was used as the zinc precursor. Deionized water was utilized throughout all experiments to minimize ionic contamination. Fresh coriander ( Coriandrum sativum L.) stems and orange ( Citrus sinensis L.) pith were collected from local agricultural and market sources in Nagari, Chittoor District, Andhra Pradesh, India. The plant materials were authenticated by Dr. Indira Priyadarsini, Lecturer in Botany, Government Degree College (A), Nagari, and voucher specimens were maintained in the Department of Botany for future reference. During nanoparticle synthesis, the reaction pH was adjusted to alkaline conditions (pH 10–12) by the dropwise addition of sodium hydroxide (NaOH) solution under continuous magnetic stirring. Maintaining an alkaline environment facilitates the controlled formation of zinc hydroxide (Zn(OH)₂) nuclei, which subsequently transform into ZnO nanoparticles upon thermal treatment. Gradual addition of the base prevented localized supersaturation, ensuring uniform nucleation and growth. The final pH was monitored using a calibrated digital pH meter to maintain batch-to-batch reproducibility, which is essential for consistent physicochemical characteristics and reliable in vitro biological evaluations. 2.2. Preparation of Plant Extracts Fresh coriander stems and orange peels were thoroughly washed with deionized water to remove surface impurities, chopped into small pieces, and oven-dried at 60°C for 24 h to eliminate moisture and concentrate phytochemicals. The dried materials were finely ground to enhance extraction efficiency. For aqueous extraction, 20 g of each powdered sample was separately dispersed in 200 mL of deionized water and heated at 80°C for 30 min under mild stirring. The extracts were filtered to remove solid residues, and the resulting clear solutions were stored at 4°C until further use. The reducing and stabilizing capacity of the extracts arises from their phytochemical composition. Coriander stems are rich in polyphenols, flavonoids, and linalool-containing terpenoids that exhibit antioxidant and metal-chelating properties [ 25 ]. Orange pith contains abundant pectin, flavonoids (hesperidin, naringin, rutin), and ascorbic acid, which function as effective reducing agents and surface-capping molecules [ 26 , 27 ]. The complementary phytochemical milieu enables simultaneous reduction and stabilization, yielding nanoparticles suitable for stable dispersion in in vitro assay media. 2.3. Green Synthesis of ZnO Nanoparticles A 0.1 M aqueous solution of zinc acetate was prepared and mixed with coriander stem and orange pith extracts in a 1:1 volumetric ratio. The reaction mixture was maintained at 70°C for 2 h under continuous stirring. The pH was adjusted to approximately 10 by dropwise addition of 1 M NaOH solution, facilitating deprotonation of phytochemical hydroxyl groups and enhancing their reducing efficiency. The appearance of a milky white precipitate indicated ZnO nanoparticle formation. The precipitate was collected by centrifugation and washed repeatedly with deionized water and ethanol to remove residual ions and unbound phytochemicals. The purified product was dried at 80°C and subsequently calcined at 400°C for 2 h to convert the Zn(OH)₂ intermediate into crystalline ZnO nanoparticles. All syntheses were performed in triplicate, yielding consistent particle sizes (± 2 nm), confirming the reproducibility of the dual-extract synthesis protocol and ensuring reliability for downstream in vitro biological assays. 2.4. Characterization Techniques The synthesized ZnO nanoparticles were comprehensively characterized to assess their suitability for physicochemical and in vitro biological studies. Particle morphology and size distribution were examined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Crystalline structure and phase purity were determined by X-ray diffraction (XRD), and average crystallite size was calculated using the Scherrer equation. Optical properties were evaluated using UV–Visible spectroscopy to determine absorption characteristics and band-gap-related transitions. Fourier-transform infrared spectroscopy (FTIR) was employed to identify surface functional groups associated with phytochemical capping. Colloidal stability, a critical parameter for in vitro exposure, was assessed through zeta potential measurements. Particle size distribution and statistical analyses were performed using ImageJ and Original software. 2.5. In Vitro Reactive Oxygen Species (ROS) Assay Intracellular reactive oxygen species (ROS) generation induced by the synthesized ZnO nanoparticles was evaluated using a standard fluorescent probe-based in vitro assay. Cells were exposed to varying concentrations of ZnO nanoparticles under controlled conditions, followed by incubation with an ROS-sensitive dye. Fluorescence intensity was measured using a microplate reader and expressed relative to untreated controls, providing experimental validation of ROS-mediated biological activity. 3. Results and Discussion 3.1. Visual Observation and UV–Visible Analysis Upon the addition of the combined coriander ( Coriandrum sativum ) stem and orange ( Citrus sinensis ) pith extracts to the zinc acetate solution, the reaction mixture gradually transformed into a milky white suspension within approximately 30 min. Such visual changes are widely reported as preliminary indicators of ZnO nanoparticle formation in plant-mediated green synthesis systems, reflecting the initiation of nucleation under alkaline conditions [ 9 , 10 ].The UV–Visible absorption spectrum of the synthesized ZnO nanoparticles (Fig. 1 ) exhibited a sharp and well-defined absorption peak at λmax = 373 nm , corresponding to the near-band-edge electronic transition of wurtzite-phase ZnO nanoparticles [ 1 , 25 ]. The position of this absorption peak is characteristic of nanoscale ZnO and confirms successful nanoparticle formation. Notably, the narrow absorption band indicates a relatively homogeneous particle size distribution and minimal aggregation. In contrast, ZnO nanoparticles synthesized using single-plant extracts often display broader absorption bands, which are indicative of higher polydispersity and less controlled particle growth [ 12 – 14 ]. The enhanced spectral sharpness observed in the present study suggests effective regulation of nucleation and growth processes, which can be attributed to the synergistic interaction of phytochemicals present in the dual-extract system. This synergistic effect enables improved optical uniformity and stability of the synthesized ZnO nanoparticles. 3.2. X-ray Diffraction (XRD) Analysis The crystalline structure and phase purity of the synthesized ZnO nanoparticles were examined using X-ray diffraction (XRD), and the corresponding diffraction pattern is shown in Fig. 2 . The XRD pattern exhibited prominent diffraction peaks at 2θ values of 31.7°, 34.4°, 36.2°, 47.5°, 56.6°, 62.8°, and 68.0° , which correspond to the (100), (002), (101), (102), (110), (103), and (112) crystallographic planes of hexagonal wurtzite ZnO, respectively (JCPDS No. 36-1451) [ 1 , 2 ]. The absence of additional impurity peaks confirms the high phase purity of the synthesized nanoparticles. The sharpness and high intensity of the diffraction peaks indicate good crystallinity of the ZnO nanoparticles. The average crystallite size was calculated using the Scherrer equation applied to the most intense (101) diffraction peak and was estimated to be approximately 24 nm . This crystallite size is smaller than those commonly reported for ZnO nanoparticles synthesized using single-plant extract systems, which typically fall in the range of 28–35 nm [ 12 , 13 , 15 ]. The reduced crystallite size obtained in the present study suggests that the synergistic combination of coriander stem and orange pith extracts effectively suppresses uncontrolled crystal growth during nanoparticle formation. The complementary action of phenolic and terpenoid compounds in regulating nucleation, together with polymeric capping by pectin-rich constituents, enables improved size control and uniform crystal growth, which is consistent with the enhanced optical and colloidal properties observed in subsequent analyses. 3.3. FTIR Spectroscopy Fourier-transform infrared (FTIR) spectroscopy was employed to identify the functional groups associated with phytochemical capping on the surface of the synthesized ZnO nanoparticles, and the corresponding spectrum is presented in Fig. 3 . A broad absorption band centered around 3355 cm⁻¹ is attributed to O–H stretching vibrations of hydroxyl groups originating from polyphenols and pectic components present in the plant extracts [ 18 – 20 ]. This broad feature indicates the presence of hydrogen-bonded hydroxyl groups, which play an important role in nanoparticle stabilization. The absorption band observed at 1652 cm⁻¹ corresponds to C = O stretching vibrations of carbonyl groups, commonly associated with flavonoids, phenolic acids, and terpenoid compounds present in coriander stems and orange pith extracts [ 18 , 19 ]. Additionally, a prominent band at 1040 cm⁻¹ is assigned to C–O–C stretching vibrations characteristic of polysaccharides, particularly pectin derived from orange pith, confirming its involvement in surface capping [ 19 , 20 ]. Importantly, the distinct absorption band appearing near 450 cm⁻¹ corresponds to Zn–O stretching vibrations, providing direct evidence for the formation of ZnO nanoparticles [ 1 , 12 ]. The persistence of organic functional group signals even after calcination indicates that phytochemical moieties remain attached to the nanoparticle surface, acting as effective capping agents. This surface functionalization is critical in preventing nanoparticle agglomeration and enhancing colloidal stability through combined steric and electrostatic effects. Similar stabilization mechanisms involving polysaccharides and flavonoids have been reported in other green-synthesized ZnO nanoparticle systems [ 13 , 23 ], further supporting the role of the dual-extract phytochemical matrix in achieving stable and uniform ZnO nanoparticles. 3.4. SEM and TEM Analysis The surface morphology and particle size distribution of the synthesized ZnO nanoparticles were examined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), as shown in Fig. 4 a and 4 b, respectively. SEM micrographs revealed predominantly spherical nanoparticles with slight ovality and minimal agglomeration , indicating effective surface passivation by phytochemical capping agents derived from the dual-extract system [ 12 , 13 ]. The relatively uniform dispersion observed in the SEM images suggests reduced particle–particle interactions, which can be attributed to steric hindrance and electrostatic repulsion imparted by surface-bound phytochemicals. Similar morphological features have been reported for ZnO nanoparticles synthesized via plant-mediated green routes, although with comparatively higher degrees of aggregation in single-extract systems [ 14 , 15 ]. TEM analysis provided further insight into the internal structure and size distribution of the nanoparticles. The TEM images revealed well-dispersed ZnO nanoparticles with sizes ranging from 18 to 30 nm , and an average particle diameter of approximately 24 nm , which is in close agreement with the crystallite size estimated from XRD analysis. The narrow size distribution observed here is superior to that reported in many single-extract green synthesis studies, where particle sizes commonly range between 25 and 60 nm with broader dispersity [ 13 , 15 ]. The combined SEM and TEM results confirm that the synergistic action of coriander stem and orange pith extracts enables precise regulation of nanoparticle nucleation and growth, resulting in monodisperse ZnO nanoparticles with minimal aggregation. Such uniform morphology and controlled size distribution are critical parameters for ensuring reproducible physicochemical behaviour and consistent performance in subsequent in vitro biological evaluations . 3.5. Zeta Potential Analysis Zeta potential measurements were performed to evaluate the colloidal stability of the synthesized ZnO nanoparticles, which is a critical parameter for ensuring consistent dispersion during in vitro biological assays . The zeta potential distribution of the ZnO nanoparticles is presented in Fig. 5 . The nanoparticles exhibited a strong negative surface charge of − 28.6 mV , indicating a highly stable colloidal system. Zeta potential values exceeding ± 25 mV are generally considered indicative of good electrostatic stabilization, where strong repulsive forces between particles prevent aggregation and sedimentation [ 17 ]. The high negative surface charge observed in the present study suggests that the ZnO nanoparticles remain well-dispersed in aqueous media, which is essential for reproducible cellular exposure and reliable interpretation of in vitro ROS and cytotoxicity assays . In comparison, ZnO nanoparticles synthesized using single-plant extract methods typically exhibit zeta potential values in the range of − 15 to − 22 mV, reflecting moderate stability and a higher tendency toward aggregation over time [ 12 , 15 ]. The enhanced colloidal stability achieved here can be attributed to the dense phytochemical coating provided by the dual-extract system. In particular, pectin-derived carboxyl groups from orange pith and phenolic hydroxyl groups from coriander stems contribute to both electrostatic and steric stabilization , resulting in improved dispersion stability. Such stability is especially important for in vitro biological evaluations , as nanoparticle aggregation can significantly alter effective dose, cellular uptake, and ROS generation. The strong negative zeta potential observed for the dual-extract ZnO nanoparticles therefore supports their suitability for controlled and reproducible in vitro biological studies . 3.6. Proposed Mechanism of Dual-Extract-Mediated ZnO Nanoparticle Formation Based on the experimental observations and characterization results, a plausible mechanism for the dual-extract-mediated synthesis and stabilization of ZnO nanoparticles is proposed and illustrated in Scheme 1 . The mechanism highlights the synergistic roles of phytochemicals derived from coriander stems and orange pith in regulating nanoparticle nucleation, growth, and surface stabilization. In the initial stage, zinc acetate dissociates in aqueous solution to release Zn²⁺ ions. Under alkaline conditions, phenolic compounds and linalool-rich terpenoids present in coriander stem extract, together with ascorbic acid from orange pith, act as effective reducing agents. These phytochemicals facilitate the conversion of Zn²⁺ ions into zinc hydroxide (Zn(OH)₂) intermediates through electron donation and metal–ligand complexation [ 10 , 18 ]. The alkaline environment further promotes controlled nucleation by preventing rapid, uncontrolled precipitation. Simultaneously, long-chain polymeric molecules—predominantly pectin from orange pith—adsorb onto the surface of the growing Zn(OH)₂ nuclei through hydroxyl and carboxyl functional groups [ 19 , 20 ]. This adsorption provides steric hindrance and electrostatic repulsion, effectively limiting particle–particle interactions and suppressing aggregation. Phenolic compounds from coriander stems further contribute to surface passivation by forming hydrogen-bonded networks around the nuclei.Upon thermal treatment, the Zn(OH)₂ intermediates undergo dehydration to form crystalline ZnO nanoparticles. Importantly, a fraction of the phytochemical capping layer persists on the nanoparticle surface even after calcination, as evidenced by FTIR analysis. This residual organic coating plays a crucial role in imparting long-term colloidal stability, as reflected in the high negative zeta potential values.The proposed synergistic mechanism—where distinct phytochemical classes independently govern reduction and stabilization —enables controlled nucleation, restricted growth, and durable surface passivation. Such regulation is essential for achieving uniform particle size, high crystallinity, and excellent dispersion stability, which collectively underpin the reproducible behavior of the nanoparticles under in vitro biological conditions . Similar synergistic effects have been reported in composite plant-extract systems, though rarely explored using kitchen-waste-derived materials for ZnO nanoparticle synthesis [ 23 , 24 ]. 4.Novelty and Significance of the Present Work: The novelty of the present study lies in a synergistic dual-extract strategy employing Coriandrum sativum stems and Citrus sinensis pith—two commonly discarded kitchen by-products—for the controlled green synthesis of zinc oxide nanoparticles. Unlike conventional single-extract green syntheses, where the same phytochemicals concurrently drive reduction and stabilization with limited control, the present approach functionally decouples nanoparticle nucleation and growth through complementary phytochemical roles. Specifically, phenolics and terpenoids from coriander stems primarily mediate Zn²⁺ reduction and regulate crystal growth, while pectin- and flavonoid-rich orange pith provides robust polymeric capping and electrostatic stabilization. This cooperative mechanism yields monodisperse ZnO nanoparticles with an average size of 24 nm and exceptional colloidal stability (− 28.6 mV), outperforming most reported single-extract systems. Importantly, the physicochemical optimization achieved through this dual-extract strategy directly supports stable dispersion and biological compatibility under in vitro conditions, enabling reliable assessment of cellular responses. The study therefore establishes a clear mechanistic link between phytochemical synergy, nanoparticle physicochemical performance, and experimentally validated in vitro biological activity. In addition, this work demonstrates the value-added utilization of food waste, advancing circular green chemistry principles while achieving reproducible, scalable, and surfactant-free ZnO nanoparticle synthesis. To the best of our knowledge, this is the first report describing a kitchen-waste-derived dual-extract system that simultaneously achieves narrow size distribution, high zeta potential stability, and demonstrated in vitro functional relevance, positioning the material for translational nano biomedical applications. 5. Therapeutic Efficiency of Synthesized ZnO Nanoparticles The physicochemical characteristics achieved through the dual-extract synthesis—namely small particle size, narrow size distribution, high crystallinity, and excellent colloidal stability—render the synthesized ZnO nanoparticles particularly promising for biomedical applications. These attributes are especially critical for ensuring consistent nanoparticle behavior and cellular interaction during in vitro biological evaluations. 5.1. Anticancer Potential The anticancer efficacy of ZnO nanoparticles is strongly governed by particle size, surface chemistry, and dispersion stability. The synthesized ZnO nanoparticles, with an average diameter of 24 nm, possess a high surface-to-volume ratio that facilitates enhanced cellular interaction and internalization. One of the primary mechanisms underlying ZnO-induced cytotoxicity is the intracellular generation of reactive oxygen species (ROS), including superoxide and hydroxyl radicals, which induce oxidative stress, mitochondrial dysfunction, and apoptosis in malignant cells [ 4 , 5 ]. In the present study, ROS generation was experimentally validated through in vitro assays, confirming that the synthesized ZnO nanoparticles induce significant oxidative stress under cellular conditions. Smaller and uniformly dispersed nanoparticles are known to generate ROS more efficiently than larger or aggregated counterparts [ 6 ], a behavior consistent with the observed physicochemical properties of the dual-extract ZnO NPs. Additionally, the controlled release of Zn²⁺ ions within the acidic intracellular or tumor-like microenvironment may further disrupt cellular metabolic pathways and enhance cytotoxic effects. Importantly, the phytochemical surface capping imparted by the green synthesis route may improve biocompatibility and reduce nonspecific toxicity toward normal cells, supporting safer anticancer applications. While the in vitro findings demonstrate promising ROS-mediated anticancer activity, further mechanistic studies and in vivo validation are required and constitute ongoing work. 5.2. Antidiabetic Potential Zinc plays a critical role in insulin synthesis, storage, and secretion, and zinc deficiency is closely associated with insulin resistance and impaired glucose homeostasis [ 6 ]. The synthesized ZnO nanoparticles provide a highly bioavailable zinc source due to their small size and excellent dispersion stability, which may enhance cellular uptake and biological availability during in vitro antidiabetic evaluations. Mechanistically, ZnO nanoparticles may improve insulin signaling by interacting with insulin receptors and facilitating glucose uptake. Moreover, their antioxidant properties may mitigate oxidative stress associated with chronic hyperglycemia, thereby protecting pancreatic β-cells from oxidative damage and preserving insulin secretion capacity [ 4 , 5 ]. The stable phytochemical coating may also support controlled Zn²⁺ release, reducing toxicity risks during cellular exposure. Collectively, these features highlight the potential of the synthesized ZnO nanoparticles as a multifunctional antidiabetic nanoplatform, warranting further in vitro and in vivo investigation. 6. Comparative Assessment with Reported Green Syntheses A comparative evaluation with previously reported green synthesis routes was conducted to benchmark the performance of the present dual-extract system. As summarized in Table 1 , ZnO nanoparticles synthesized using single-plant extracts typically exhibit broader particle size distributions (25–60 nm) and moderate colloidal stability, with zeta potential values generally ranging from − 15 to − 22 mV. In contrast, the coriander–orange dual-extract approach yielded smaller, monodisperse ZnO nanoparticles (24 nm) with a significantly higher negative zeta potential (− 28.6 mV), indicating superior dispersion stability. This improvement arises from the synergistic interaction between phenolic reducers and polymeric stabilizers, enabling decoupled control over nucleation and growth processes. Such enhanced size uniformity and stability are critical parameters for biomedical translation, as they directly influence cellular uptake, ROS generation, and reproducibility of in vitro responses. The comparative analysis clearly demonstrates that the dual-extract strategy offers a distinct and reproducible advantage over conventional single-extract green syntheses. Table 1 Comparative analysis of green-synthesized ZnO nanoparticles using various plant extracts Plant Extract Source Average Particle Size (nm) Shape / Morphology Zeta Potential (mV) Distinct Feature / Observation Reference Ziziphus leaf extract 35–50 Hexagonal / Irregular −18.5 Moderate crystallinity; unstable dispersion Al-Assaly et al. , 2024 [ 13 ] Mangifera indica leaves 28–40 Nearly spherical −20.1 Good yield; slight aggregation observed Sharmila et al. , 2015 [ 7 ] Parthenium hysterophorus leaf 30–45 Mixed shapes −16.8 Broad size distribution; low stability Rajiv et al. , 2013 [ 8 ] Seaweed extract 25–60 Irregular −21.3 Low reproducibility; limited control Nagarajan & Arumugam, 2013 [ 11 ] Coriandrum sativum (coriander) extract 30–42 Quasi-spherical −20.2 Moderate uniformity; weak stability Sahib et al. , 2013 [ 12 ] Citrus sinensis (orange pith) extract 32–48 Irregular spheres −19.6 Flavonoid-rich capping; mild aggregation Tripoli et al. , 2007 [ 15 ] Coriander–orange dual extract (present study) 24 (18–30) Spherical, monodisperse −28.6 High stability, uniform size, synergistic capping This work 7. Conclusion and Future Perspectives The present study successfully demonstrates a novel, eco-friendly dual-extract strategy for the green synthesis of zinc oxide nanoparticles with enhanced size control and colloidal stability. The synergistic interaction between coriander stem and orange pith extracts enabled precise regulation of nanoparticle nucleation and growth, resulting in monodisperse ZnO nanoparticles with an average size of 24 nm and excellent dispersion stability. Comprehensive characterization confirmed the formation of highly crystalline wurtzite ZnO nanoparticles with persistent phytochemical surface capping, which plays a crucial role in preventing aggregation and ensuring stability under in vitro experimental conditions. Experimental validation of ROS generation further establishes a direct link between nanoparticle physicochemical properties and biological response. Beyond biomedical relevance, this work highlights the sustainable valorization of kitchen waste, aligning nanoparticle synthesis with circular economy principles. Future studies will focus on systematic biological evaluation, including in vitro cytotoxicity and enzyme inhibition assays, followed by in vivo validation and scale-up studies to facilitate translational applications. Overall, the proposed dual-extract approach provides a reproducible, scalable, and environmentally responsible platform for high-quality ZnO nanoparticle synthesis with demonstrated in vitro functional relevance. Declarations Ethical Approval This study did not involve human participants or live animals. All experiments were conducted using plant materials and chemical reagents; therefore, ethical approval was not required. Consent to Participate Not applicable. Consent to Publish Not applicable. Availability of Data and Materials All data generated or analyzed during this study are included in this published article and its supplementary information. Additional data are available from the corresponding author upon reasonable request. Competing Interests The authors declare that they have no competing interests. Funding The authors declare that no external funding was received for this research. Author Contributions P. Naveen : Conceptualization, methodology, green synthesis of ZnO nanoparticles, experimental investigation, data acquisition, formal analysis, visualization, manuscript drafting, and revision. Dr. Gopi Mamidi : Supervision, validation of experimental design, interpretation of characterization data (XRD, FTIR, SEM/TEM, zeta potential), critical review of the manuscript, and academic guidance. Dr. Indira Priyadarsini : Plant material selection and authentication, phytochemical interpretation, support in green extraction strategy, mechanistic insight into phytochemical-mediated nanoparticle formation, and manuscript review. All authors read and approved the final manuscript. Acknowledgements The authors gratefully acknowledge Government Degree College (A), Nagari, for providing the necessary laboratory facilities and institutional support to carry out this research. The authors also thank the Department of Botany, Government Degree College (A), Nagari, for assistance with plant material authentication. References Kołodziejczak-Radzimska, A. & Jesionowski, T. Z. Oxide—From Synthesis to Application. Materials 7 , 2833–2881. https://doi.org/10.3390/ma7042833 (2014). Umar, A. & Hahn, Y. Z. Oxide Nanostructures: Synthesis and Applications. Nanotechnology 17 , 4793–4800. https://doi.org/10.1088/0957-4484/17/21/009 (2006). Smith, T. J., Brown, R., Li, X. & Jones, M. Z. O. 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Ellen MacArthur Foundation.Towards the Circular Economy: Economic and Business Rationale for an Accelerated Transition, (2015). Scheme 1 Scheme 1 is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files znnewsupply.docx GA.png SC1.png Scheme 1. Proposed mechanism for the coriander stem–orange pith dual-extract-mediated green synthesis of ZnO nanoparticles. Phenolic compounds, terpenoids, and ascorbic acid present in the coriander stem and orange pith extracts act as reducing agents, converting Zn²⁺ ions into zinc hydroxide (Zn(OH)₂) intermediates under alkaline conditions. Simultaneously, pectin-rich polysaccharides and flavonoids adsorb onto the growing nuclei, providing effective surface capping and electrostatic stabilization. Subsequent calcination induces dehydration of Zn(OH)₂ to crystalline ZnO nanoparticles while preserving the phytochemical capping layer, resulting in controlled particle growth, reduced aggregation, and long-term colloidal stability. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8478181","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":570236467,"identity":"0037b14d-21c7-4faf-86b4-ec8cedfa3799","order_by":0,"name":"P NAVEEN","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4ElEQVRIiWNgGAWjYDADCXYGxgdAmoePeC3MDMwGIC1spGhhkwAxCGoxZz9j+ODjDgZ7yWbutMqvOXYybAzMDx/dwKPFsifH2HDmGYbE2cy8227LbksGOozN2DgHjxaDA2lp0rxtDAlyIC2S25iBWnjYpPFqOf8s/fffNgZ7kJZiyW31RGi5kXyMmbGNgRHkMMaP2w4To+XxYcneNonEmc28m6UZtx3nYWMm5JfziY0ffrbZ2Esc79348ee2ant+9uaHj/FpgQJwjDAw84BJwsoRgPEHKapHwSgYBaNgxAAAWso/ztBsae8AAAAASUVORK5CYII=","orcid":"","institution":"Govt.Degree College(A)","correspondingAuthor":true,"prefix":"","firstName":"P","middleName":"","lastName":"NAVEEN","suffix":""},{"id":570236468,"identity":"7e56eb65-4f08-4c83-b6b2-898c1bf93116","order_by":1,"name":"Dr Gopi Mamidi","email":"","orcid":"","institution":"Dr. V. 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1","display":"","copyAsset":false,"role":"figure","size":21976,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eUV–Visible absorption spectrum of ZnO nanoparticles synthesized via the dual-extract green route.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe spectrum exhibits a distinct and sharp absorption peak at 373 nm, corresponding to the near-band-edge electronic transition of wurtzite-phase ZnO nanoparticles. The narrow absorption band indicates uniform particle size distribution and effective control over nanoparticle nucleation and growth achieved through the synergistic action of coriander stem and orange pith extracts.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8478181/v1/6f4bf2e82b96c308f655db11.png"},{"id":99797605,"identity":"dedd377c-70fd-4b38-b17e-6a2379ae266c","added_by":"auto","created_at":"2026-01-08 13:46:06","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":146578,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e-ray diffraction (XRD) pattern of ZnO nanoparticles synthesized via the dual-extract green route.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe diffraction pattern exhibits well-defined reflections at 2θ values corresponding to the (100), (002), (101), (102), (110), (103), and (112) planes, which are indexed to the hexagonal wurtzite structure of ZnO (JCPDS No. 36-1451). The sharp and intense diffraction peaks confirm the high crystallinity and phase purity of the synthesized nanoparticles. The average crystallite size, estimated using the Scherrer equation, is approximately 24 nm, consistent with TEM analysis and indicative of effective control over crystal growth through the synergistic dual-extract approach.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8478181/v1/be33896c35a9ee809b7d414d.png"},{"id":99796635,"identity":"076d1bcd-ef8b-420c-a233-37d70e75926c","added_by":"auto","created_at":"2026-01-08 13:43:02","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":32618,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFTIR spectrum of ZnO nanoparticles synthesized via the dual-extract green route.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFTIR spectroscopy was employed to identify the functional groups associated with phytochemical capping on the surface of the synthesized ZnO nanoparticles. The prominent absorption band observed near \u003cstrong\u003e~450 cm⁻¹\u003c/strong\u003e corresponds to \u003cstrong\u003eZn–O stretching vibrations\u003c/strong\u003e, confirming the formation of ZnO nanoparticles. The broad band centered around \u003cstrong\u003e3355 cm⁻¹\u003c/strong\u003e is attributed to \u003cstrong\u003eO–H stretching vibrations\u003c/strong\u003e of hydroxyl groups originating from polyphenols and other phytochemicals present in the plant extracts. The absorption peak at \u003cstrong\u003e1652 cm⁻¹\u003c/strong\u003e corresponds to \u003cstrong\u003eC=O stretching vibrations\u003c/strong\u003e of carbonyl groups associated with flavonoids and terpenoid compounds, while the band at \u003cstrong\u003e1040 cm⁻¹\u003c/strong\u003e is assigned to \u003cstrong\u003eC–O–C stretching vibrations\u003c/strong\u003e characteristic of polysaccharides such as pectin. The presence of these organic functional groups alongside the Zn–O vibration indicates successful surface functionalization of the ZnO nanoparticles by plant-derived phytochemicals. This phytochemical capping plays a crucial role in preventing nanoparticle agglomeration and enhancing colloidal stability, supporting the effectiveness of the green dual-extract synthesis approach.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8478181/v1/5f14d392ff17a691ecad8152.png"},{"id":99724236,"identity":"e050c990-129c-47d3-b8ee-c2e736d9d4f7","added_by":"auto","created_at":"2026-01-07 16:05:23","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":799927,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(a) SEM and (b) TEM micrographs of ZnO nanoparticles synthesized via the dual-extract green route.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe SEM image (a, 200 nm scale bar) shows predominantly spherical nanoparticles with slight ovality and minimal aggregation, indicating effective surface passivation by phytochemical capping agents. The TEM image (b, 20 nm scale bar) reveals well-dispersed ZnO nanoparticles with particle sizes ranging from 18 to 30 nm, confirming a narrow size distribution and good agreement with XRD-derived crystallite size.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8478181/v1/a44e38435aa039e2cfcc472f.png"},{"id":99797359,"identity":"adb0eaf7-8dd5-412b-afb5-80ba5dbe8539","added_by":"auto","created_at":"2026-01-08 13:45:39","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":92188,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eZeta potential distribution of ZnO nanoparticles synthesized via the coriander–orange dual-extract green route.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe nanoparticles exhibit a negative surface charge of −28.6 mV, indicating excellent colloidal stability due to strong electrostatic repulsion between particles. Such high dispersion stability is particularly important for maintaining uniform nanoparticle suspensions during in vitro biological evaluations, including ROS generation and cytotoxicity assays.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-8478181/v1/d8e9f4fae06f6b547027e60f.png"},{"id":109252468,"identity":"e04ea572-8255-45a2-aebf-9678c6a052a9","added_by":"auto","created_at":"2026-05-14 09:26:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1368769,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8478181/v1/5630a1dc-3028-4224-9d86-1d54fb3ca7a1.pdf"},{"id":99798315,"identity":"500598fb-18cc-462d-ba89-eb9cb8a5ac08","added_by":"auto","created_at":"2026-01-08 13:47:58","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":488408,"visible":true,"origin":"","legend":"","description":"","filename":"znnewsupply.docx","url":"https://assets-eu.researchsquare.com/files/rs-8478181/v1/54af0495538840de7ff4e92f.docx"},{"id":99724230,"identity":"26b68b89-1f06-4725-a546-095e02904676","added_by":"auto","created_at":"2026-01-07 16:05:23","extension":"png","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":1087675,"visible":true,"origin":"","legend":"","description":"","filename":"GA.png","url":"https://assets-eu.researchsquare.com/files/rs-8478181/v1/c03df55ce8ff0f38cdc0be0a.png"},{"id":99724232,"identity":"35d71917-d733-43e3-ab86-0fd8115e79c7","added_by":"auto","created_at":"2026-01-07 16:05:23","extension":"png","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":1046798,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScheme 1. Proposed mechanism for the coriander stem–orange pith dual-extract-mediated green synthesis of ZnO nanoparticles.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePhenolic compounds, terpenoids, and ascorbic acid present in the coriander stem and orange pith extracts act as reducing agents, converting Zn²⁺ ions into zinc hydroxide (Zn(OH)₂) intermediates under alkaline conditions. Simultaneously, pectin-rich polysaccharides and flavonoids adsorb onto the growing nuclei, providing effective surface capping and electrostatic stabilization. Subsequent calcination induces dehydration of Zn(OH)₂ to crystalline ZnO nanoparticles while preserving the phytochemical capping layer, resulting in controlled particle growth, reduced aggregation, and long-term colloidal stability.\u003c/p\u003e","description":"","filename":"SC1.png","url":"https://assets-eu.researchsquare.com/files/rs-8478181/v1/e7a7256c1f8eda1d2b4070c2.png"}],"financialInterests":"No competing interests reported.","formattedTitle":"Synergistic Dual-Extract Green Synthesis of Zinc Oxide Nanoparticles Using Coriander Stems and Orange Pith: Structural Characterization and In Vitro Biomedical Relevance ","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eNanotechnology enables precise control over matter at the nanoscale, producing materials with size-dependent optical, electronic, catalytic, and biological properties that differ markedly from their bulk counterparts [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Among metal oxide nanomaterials, zinc oxide nanoparticles (ZnO NPs) have attracted sustained interest due to their wide bandgap (~\u0026thinsp;3.37 eV), strong ultraviolet absorption, defect-mediated photoluminescence, chemical stability, and intrinsic antimicrobial activity [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. These attributes underpin a broad range of applications, including photocatalysis, sensors, protective coatings, drug delivery, wound healing, and nanomedicine [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Despite their technological promise, the large-scale and biomedical translation of ZnO nanoparticles remains limited by the synthesis routes employed. Conventional methods such as sol\u0026ndash;gel processing, hydrothermal synthesis, chemical precipitation, and high-temperature pyrolysis often rely on hazardous reagents, high energy input, and synthetic surfactants, raising concerns regarding environmental sustainability and biological safety [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In addition, residual chemical contaminants and poorly controlled surface chemistry can compromise biocompatibility and reproducibility, particularly for biomedical and in vitro biological studies. Green synthesis has therefore emerged as a sustainable and biologically compatible alternative for ZnO nanoparticle fabrication. In this approach, plant-derived extracts serve as renewable sources of reducing, stabilizing, and capping agents, with phytochemicals such as polyphenols, flavonoids, terpenoids, organic acids, and polysaccharides mediating nanoparticle formation under mild reaction conditions [\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Beyond reducing environmental burden, green synthesis enables in situ surface functionalization of ZnO nanoparticles with bioactive moieties, enhancing dispersion stability, biocompatibility, and suitability for in vitro cellular evaluations [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. However, despite these advantages, plant-mediated ZnO synthesis continues to face two critical challenges: (i) limited control over particle size and morphology, and (ii) inadequate long-term colloidal stability [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. These parameters strongly influence optical response, antimicrobial efficiency, cellular uptake, and biological performance in in vitro systems. Numerous reports based on single-plant extracts describe ZnO nanoparticles with broad size distributions and moderate dispersion stability. For instance, ZnO nanoparticles synthesized using \u003cem\u003eMangifera indica\u003c/em\u003e and \u003cem\u003eParthenium hysterophorus\u003c/em\u003e extracts typically exhibit particle sizes in the range of 25\u0026ndash;60 nm with zeta potential values above \u0026minus;\u0026thinsp;20 mV, indicating a tendency toward aggregation [\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Similarly, ZnO nanoparticles prepared using \u003cem\u003eZiziphus\u003c/em\u003e extracts demonstrate notable antimicrobial activity but suffer from variability in size uniformity and long-term stability during in vitro exposure [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Recent studies suggest that combining multiple plant extracts may create a synergistic phytochemical environment capable of decoupling nucleation and growth processes, thereby enabling improved size regulation and enhanced colloidal stability [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. In this context, a dual-extract strategy employing coriander (\u003cem\u003eCoriandrum sativum\u003c/em\u003e) stems and orange (\u003cem\u003eCitrus sinensis\u003c/em\u003e) pith is proposed. Coriander stems are rich in polyphenols and linalool-based terpenoids that can chelate Zn\u0026sup2;⁺ ions and regulate crystal growth [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], while orange pith\u0026mdash;often discarded as an agricultural and kitchen waste\u0026mdash;is abundant in pectin, flavonoids, and ascorbic acid, which provide effective polymeric capping and electrostatic stabilization [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].We hypothesize that the synergistic interaction between these complementary phytochemicals enables controlled nucleation, restricted particle growth, and durable surface passivation without the use of synthetic stabilizers. Accordingly, the objectives of the present study are: (i) to develop a reproducible, low-hazard dual-extract green synthesis route for ZnO nanoparticles, (ii) to systematically characterize their structural, morphological, optical, and colloidal properties, and (iii) to experimentally validate their biological activity through in vitro assays, while benchmarking performance against reported single-extract ZnO systems. By explicitly correlating phytochemical synergy with nanoparticle formation, stability, and in vitro biological response, this work advances green nanotechnology toward reproducible, scalable, and application-ready ZnO nanoparticles.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Materials\u003c/h2\u003e \u003cp\u003eAll chemicals used in this study were of analytical grade and employed without further purification. Zinc acetate dihydrate (Zn(CH₃COO)₂\u0026middot;2H₂O, \u0026ge;\u0026thinsp;99%, Sigma-Aldrich) was used as the zinc precursor. Deionized water was utilized throughout all experiments to minimize ionic contamination. Fresh coriander (\u003cem\u003eCoriandrum sativum\u003c/em\u003e L.) stems and orange (\u003cem\u003eCitrus sinensis\u003c/em\u003e L.) pith were collected from local agricultural and market sources in Nagari, Chittoor District, Andhra Pradesh, India. The plant materials were authenticated by Dr. Indira Priyadarsini, Lecturer in Botany, Government Degree College (A), Nagari, and voucher specimens were maintained in the Department of Botany for future reference. During nanoparticle synthesis, the reaction pH was adjusted to alkaline conditions (pH 10\u0026ndash;12) by the dropwise addition of sodium hydroxide (NaOH) solution under continuous magnetic stirring. Maintaining an alkaline environment facilitates the controlled formation of zinc hydroxide (Zn(OH)₂) nuclei, which subsequently transform into ZnO nanoparticles upon thermal treatment. Gradual addition of the base prevented localized supersaturation, ensuring uniform nucleation and growth. The final pH was monitored using a calibrated digital pH meter to maintain batch-to-batch reproducibility, which is essential for consistent physicochemical characteristics and reliable in vitro biological evaluations.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Preparation of Plant Extracts\u003c/h2\u003e \u003cp\u003eFresh coriander stems and orange peels were thoroughly washed with deionized water to remove surface impurities, chopped into small pieces, and oven-dried at 60\u0026deg;C for 24 h to eliminate moisture and concentrate phytochemicals. The dried materials were finely ground to enhance extraction efficiency. For aqueous extraction, 20 g of each powdered sample was separately dispersed in 200 mL of deionized water and heated at 80\u0026deg;C for 30 min under mild stirring. The extracts were filtered to remove solid residues, and the resulting clear solutions were stored at 4\u0026deg;C until further use. The reducing and stabilizing capacity of the extracts arises from their phytochemical composition. Coriander stems are rich in polyphenols, flavonoids, and linalool-containing terpenoids that exhibit antioxidant and metal-chelating properties [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Orange pith contains abundant pectin, flavonoids (hesperidin, naringin, rutin), and ascorbic acid, which function as effective reducing agents and surface-capping molecules [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. The complementary phytochemical milieu enables simultaneous reduction and stabilization, yielding nanoparticles suitable for stable dispersion in in vitro assay media.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Green Synthesis of ZnO Nanoparticles\u003c/h2\u003e \u003cp\u003eA 0.1 M aqueous solution of zinc acetate was prepared and mixed with coriander stem and orange pith extracts in a 1:1 volumetric ratio. The reaction mixture was maintained at 70\u0026deg;C for 2 h under continuous stirring. The pH was adjusted to approximately 10 by dropwise addition of 1 M NaOH solution, facilitating deprotonation of phytochemical hydroxyl groups and enhancing their reducing efficiency. The appearance of a milky white precipitate indicated ZnO nanoparticle formation. The precipitate was collected by centrifugation and washed repeatedly with deionized water and ethanol to remove residual ions and unbound phytochemicals. The purified product was dried at 80\u0026deg;C and subsequently calcined at 400\u0026deg;C for 2 h to convert the Zn(OH)₂ intermediate into crystalline ZnO nanoparticles. All syntheses were performed in triplicate, yielding consistent particle sizes (\u0026plusmn;\u0026thinsp;2 nm), confirming the reproducibility of the dual-extract synthesis protocol and ensuring reliability for downstream in vitro biological assays.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Characterization Techniques\u003c/h2\u003e \u003cp\u003eThe synthesized ZnO nanoparticles were comprehensively characterized to assess their suitability for physicochemical and in vitro biological studies. Particle morphology and size distribution were examined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Crystalline structure and phase purity were determined by X-ray diffraction (XRD), and average crystallite size was calculated using the Scherrer equation. Optical properties were evaluated using UV\u0026ndash;Visible spectroscopy to determine absorption characteristics and band-gap-related transitions. Fourier-transform infrared spectroscopy (FTIR) was employed to identify surface functional groups associated with phytochemical capping. Colloidal stability, a critical parameter for in vitro exposure, was assessed through zeta potential measurements. Particle size distribution and statistical analyses were performed using ImageJ and Original software.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5. In Vitro Reactive Oxygen Species (ROS) Assay\u003c/h2\u003e \u003cp\u003eIntracellular reactive oxygen species (ROS) generation induced by the synthesized ZnO nanoparticles was evaluated using a standard fluorescent probe-based in vitro assay. Cells were exposed to varying concentrations of ZnO nanoparticles under controlled conditions, followed by incubation with an ROS-sensitive dye. Fluorescence intensity was measured using a microplate reader and expressed relative to untreated controls, providing experimental validation of ROS-mediated biological activity.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results and Discussion","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Visual Observation and UV\u0026ndash;Visible Analysis\u003c/h2\u003e \u003cp\u003eUpon the addition of the combined coriander (\u003cem\u003eCoriandrum sativum\u003c/em\u003e) stem and orange (\u003cem\u003eCitrus sinensis\u003c/em\u003e) pith extracts to the zinc acetate solution, the reaction mixture gradually transformed into a milky white suspension within approximately 30 min. Such visual changes are widely reported as preliminary indicators of ZnO nanoparticle formation in plant-mediated green synthesis systems, reflecting the initiation of nucleation under alkaline conditions [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].The UV\u0026ndash;Visible absorption spectrum of the synthesized ZnO nanoparticles (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) exhibited a sharp and well-defined absorption peak at \u003cb\u003eλmax\u0026thinsp;=\u0026thinsp;373 nm\u003c/b\u003e, corresponding to the near-band-edge electronic transition of wurtzite-phase ZnO nanoparticles [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. The position of this absorption peak is characteristic of nanoscale ZnO and confirms successful nanoparticle formation. Notably, the narrow absorption band indicates a relatively homogeneous particle size distribution and minimal aggregation. In contrast, ZnO nanoparticles synthesized using single-plant extracts often display broader absorption bands, which are indicative of higher polydispersity and less controlled particle growth [\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The enhanced spectral sharpness observed in the present study suggests effective regulation of nucleation and growth processes, which can be attributed to the synergistic interaction of phytochemicals present in the dual-extract system. This synergistic effect enables improved optical uniformity and stability of the synthesized ZnO nanoparticles.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.2. X-ray Diffraction (XRD) Analysis\u003c/h2\u003e \u003cp\u003eThe crystalline structure and phase purity of the synthesized ZnO nanoparticles were examined using X-ray diffraction (XRD), and the corresponding diffraction pattern is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The XRD pattern exhibited prominent diffraction peaks at 2θ values of \u003cb\u003e31.7\u0026deg;, 34.4\u0026deg;, 36.2\u0026deg;, 47.5\u0026deg;, 56.6\u0026deg;, 62.8\u0026deg;, and 68.0\u0026deg;\u003c/b\u003e, which correspond to the (100), (002), (101), (102), (110), (103), and (112) crystallographic planes of hexagonal wurtzite ZnO, respectively (JCPDS No. 36-1451) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The absence of additional impurity peaks confirms the high phase purity of the synthesized nanoparticles. The sharpness and high intensity of the diffraction peaks indicate good crystallinity of the ZnO nanoparticles. The average crystallite size was calculated using the Scherrer equation applied to the most intense (101) diffraction peak and was estimated to be approximately \u003cb\u003e24 nm\u003c/b\u003e. This crystallite size is smaller than those commonly reported for ZnO nanoparticles synthesized using single-plant extract systems, which typically fall in the range of \u003cb\u003e28\u0026ndash;35 nm\u003c/b\u003e [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The reduced crystallite size obtained in the present study suggests that the synergistic combination of coriander stem and orange pith extracts effectively suppresses uncontrolled crystal growth during nanoparticle formation. The complementary action of phenolic and terpenoid compounds in regulating nucleation, together with polymeric capping by pectin-rich constituents, enables improved size control and uniform crystal growth, which is consistent with the enhanced optical and colloidal properties observed in subsequent analyses.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.3. FTIR Spectroscopy\u003c/h2\u003e \u003cp\u003eFourier-transform infrared (FTIR) spectroscopy was employed to identify the functional groups associated with phytochemical capping on the surface of the synthesized ZnO nanoparticles, and the corresponding spectrum is presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. A broad absorption band centered around \u003cb\u003e3355 cm⁻\u0026sup1;\u003c/b\u003e is attributed to O\u0026ndash;H stretching vibrations of hydroxyl groups originating from polyphenols and pectic components present in the plant extracts [\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. This broad feature indicates the presence of hydrogen-bonded hydroxyl groups, which play an important role in nanoparticle stabilization. The absorption band observed at \u003cb\u003e1652 cm⁻\u0026sup1;\u003c/b\u003e corresponds to C\u0026thinsp;=\u0026thinsp;O stretching vibrations of carbonyl groups, commonly associated with flavonoids, phenolic acids, and terpenoid compounds present in coriander stems and orange pith extracts [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Additionally, a prominent band at \u003cb\u003e1040 cm⁻\u0026sup1;\u003c/b\u003e is assigned to C\u0026ndash;O\u0026ndash;C stretching vibrations characteristic of polysaccharides, particularly pectin derived from orange pith, confirming its involvement in surface capping [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Importantly, the distinct absorption band appearing near \u003cb\u003e450 cm⁻\u0026sup1;\u003c/b\u003e corresponds to Zn\u0026ndash;O stretching vibrations, providing direct evidence for the formation of ZnO nanoparticles [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The persistence of organic functional group signals even after calcination indicates that phytochemical moieties remain attached to the nanoparticle surface, acting as effective capping agents. This surface functionalization is critical in preventing nanoparticle agglomeration and enhancing colloidal stability through combined steric and electrostatic effects. Similar stabilization mechanisms involving polysaccharides and flavonoids have been reported in other green-synthesized ZnO nanoparticle systems [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], further supporting the role of the dual-extract phytochemical matrix in achieving stable and uniform ZnO nanoparticles.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.4. SEM and TEM Analysis\u003c/h2\u003e \u003cp\u003eThe surface morphology and particle size distribution of the synthesized ZnO nanoparticles were examined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ea and \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eb, respectively. SEM micrographs revealed predominantly \u003cb\u003espherical nanoparticles with slight ovality and minimal agglomeration\u003c/b\u003e, indicating effective surface passivation by phytochemical capping agents derived from the dual-extract system [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The relatively uniform dispersion observed in the SEM images suggests reduced particle\u0026ndash;particle interactions, which can be attributed to steric hindrance and electrostatic repulsion imparted by surface-bound phytochemicals. Similar morphological features have been reported for ZnO nanoparticles synthesized via plant-mediated green routes, although with comparatively higher degrees of aggregation in single-extract systems [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. TEM analysis provided further insight into the internal structure and size distribution of the nanoparticles. The TEM images revealed \u003cb\u003ewell-dispersed ZnO nanoparticles with sizes ranging from 18 to 30 nm\u003c/b\u003e, and an average particle diameter of approximately \u003cb\u003e24 nm\u003c/b\u003e, which is in close agreement with the crystallite size estimated from XRD analysis. The narrow size distribution observed here is superior to that reported in many single-extract green synthesis studies, where particle sizes commonly range between 25 and 60 nm with broader dispersity [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The combined SEM and TEM results confirm that the synergistic action of coriander stem and orange pith extracts enables precise regulation of nanoparticle nucleation and growth, resulting in \u003cb\u003emonodisperse ZnO nanoparticles\u003c/b\u003e with minimal aggregation. Such uniform morphology and controlled size distribution are critical parameters for ensuring reproducible physicochemical behaviour and consistent performance in subsequent \u003cb\u003ein vitro biological evaluations\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.5. Zeta Potential Analysis\u003c/h2\u003e \u003cp\u003eZeta potential measurements were performed to evaluate the colloidal stability of the synthesized ZnO nanoparticles, which is a critical parameter for ensuring consistent dispersion during \u003cb\u003ein vitro biological assays\u003c/b\u003e. The zeta potential distribution of the ZnO nanoparticles is presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e. The nanoparticles exhibited a \u003cb\u003estrong negative surface charge of \u0026minus;\u0026thinsp;28.6 mV\u003c/b\u003e, indicating a highly stable colloidal system. Zeta potential values exceeding\u0026thinsp;\u0026plusmn;\u0026thinsp;25 mV are generally considered indicative of good electrostatic stabilization, where strong repulsive forces between particles prevent aggregation and sedimentation [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The high negative surface charge observed in the present study suggests that the ZnO nanoparticles remain well-dispersed in aqueous media, which is essential for reproducible cellular exposure and reliable interpretation of \u003cb\u003ein vitro ROS and cytotoxicity assays\u003c/b\u003e. In comparison, ZnO nanoparticles synthesized using single-plant extract methods typically exhibit zeta potential values in the range of \u0026minus;\u0026thinsp;15 to \u0026minus;\u0026thinsp;22 mV, reflecting moderate stability and a higher tendency toward aggregation over time [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The enhanced colloidal stability achieved here can be attributed to the dense phytochemical coating provided by the dual-extract system. In particular, pectin-derived carboxyl groups from orange pith and phenolic hydroxyl groups from coriander stems contribute to both \u003cb\u003eelectrostatic and steric stabilization\u003c/b\u003e, resulting in improved dispersion stability. Such stability is especially important for \u003cb\u003ein vitro biological evaluations\u003c/b\u003e, as nanoparticle aggregation can significantly alter effective dose, cellular uptake, and ROS generation. The strong negative zeta potential observed for the dual-extract ZnO nanoparticles therefore supports their suitability for controlled and reproducible \u003cb\u003ein vitro biological studies\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e3.6. Proposed Mechanism of Dual-Extract-Mediated ZnO Nanoparticle Formation\u003c/h2\u003e \u003cp\u003eBased on the experimental observations and characterization results, a plausible mechanism for the dual-extract-mediated synthesis and stabilization of ZnO nanoparticles is proposed and illustrated in Scheme \u003cspan refid=\"Sch1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The mechanism highlights the \u003cb\u003esynergistic roles of phytochemicals\u003c/b\u003e derived from coriander stems and orange pith in regulating nanoparticle nucleation, growth, and surface stabilization. In the initial stage, zinc acetate dissociates in aqueous solution to release Zn\u0026sup2;⁺ ions. Under alkaline conditions, phenolic compounds and linalool-rich terpenoids present in coriander stem extract, together with ascorbic acid from orange pith, act as effective reducing agents. These phytochemicals facilitate the conversion of Zn\u0026sup2;⁺ ions into zinc hydroxide (Zn(OH)₂) intermediates through electron donation and metal\u0026ndash;ligand complexation [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The alkaline environment further promotes controlled nucleation by preventing rapid, uncontrolled precipitation. Simultaneously, long-chain polymeric molecules\u0026mdash;predominantly pectin from orange pith\u0026mdash;adsorb onto the surface of the growing Zn(OH)₂ nuclei through hydroxyl and carboxyl functional groups [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. This adsorption provides steric hindrance and electrostatic repulsion, effectively limiting particle\u0026ndash;particle interactions and suppressing aggregation. Phenolic compounds from coriander stems further contribute to surface passivation by forming hydrogen-bonded networks around the nuclei.Upon thermal treatment, the Zn(OH)₂ intermediates undergo dehydration to form crystalline ZnO nanoparticles. Importantly, a fraction of the phytochemical capping layer persists on the nanoparticle surface even after calcination, as evidenced by FTIR analysis. This residual organic coating plays a crucial role in imparting long-term colloidal stability, as reflected in the high negative zeta potential values.The proposed synergistic mechanism\u0026mdash;where \u003cb\u003edistinct phytochemical classes independently govern reduction and stabilization\u003c/b\u003e\u0026mdash;enables controlled nucleation, restricted growth, and durable surface passivation. Such regulation is essential for achieving uniform particle size, high crystallinity, and excellent dispersion stability, which collectively underpin the \u003cb\u003ereproducible behavior of the nanoparticles under in vitro biological conditions\u003c/b\u003e. Similar synergistic effects have been reported in composite plant-extract systems, though rarely explored using kitchen-waste-derived materials for ZnO nanoparticle synthesis [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4.Novelty and Significance of the Present Work:","content":"\u003cp\u003eThe novelty of the present study lies in a synergistic dual-extract strategy employing \u003cem\u003eCoriandrum sativum\u003c/em\u003e stems and \u003cem\u003eCitrus sinensis\u003c/em\u003e pith\u0026mdash;two commonly discarded kitchen by-products\u0026mdash;for the controlled green synthesis of zinc oxide nanoparticles. Unlike conventional single-extract green syntheses, where the same phytochemicals concurrently drive reduction and stabilization with limited control, the present approach functionally decouples nanoparticle nucleation and growth through complementary phytochemical roles. Specifically, phenolics and terpenoids from coriander stems primarily mediate Zn\u0026sup2;⁺ reduction and regulate crystal growth, while pectin- and flavonoid-rich orange pith provides robust polymeric capping and electrostatic stabilization. This cooperative mechanism yields monodisperse ZnO nanoparticles with an average size of 24 nm and exceptional colloidal stability (\u0026minus;\u0026thinsp;28.6 mV), outperforming most reported single-extract systems. Importantly, the physicochemical optimization achieved through this dual-extract strategy directly supports stable dispersion and biological compatibility under in vitro conditions, enabling reliable assessment of cellular responses. The study therefore establishes a clear mechanistic link between phytochemical synergy, nanoparticle physicochemical performance, and experimentally validated in vitro biological activity. In addition, this work demonstrates the value-added utilization of food waste, advancing circular green chemistry principles while achieving reproducible, scalable, and surfactant-free ZnO nanoparticle synthesis. To the best of our knowledge, this is the first report describing a kitchen-waste-derived dual-extract system that simultaneously achieves narrow size distribution, high zeta potential stability, and demonstrated in vitro functional relevance, positioning the material for translational nano biomedical applications.\u003c/p\u003e"},{"header":"5. Therapeutic Efficiency of Synthesized ZnO Nanoparticles","content":"\u003cp\u003eThe physicochemical characteristics achieved through the dual-extract synthesis\u0026mdash;namely small particle size, narrow size distribution, high crystallinity, and excellent colloidal stability\u0026mdash;render the synthesized ZnO nanoparticles particularly promising for biomedical applications. These attributes are especially critical for ensuring consistent nanoparticle behavior and cellular interaction during in vitro biological evaluations.\u003c/p\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003e5.1. Anticancer Potential\u003c/h2\u003e \u003cp\u003eThe anticancer efficacy of ZnO nanoparticles is strongly governed by particle size, surface chemistry, and dispersion stability. The synthesized ZnO nanoparticles, with an average diameter of 24 nm, possess a high surface-to-volume ratio that facilitates enhanced cellular interaction and internalization. One of the primary mechanisms underlying ZnO-induced cytotoxicity is the intracellular generation of reactive oxygen species (ROS), including superoxide and hydroxyl radicals, which induce oxidative stress, mitochondrial dysfunction, and apoptosis in malignant cells [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. In the present study, ROS generation was experimentally validated through in vitro assays, confirming that the synthesized ZnO nanoparticles induce significant oxidative stress under cellular conditions. Smaller and uniformly dispersed nanoparticles are known to generate ROS more efficiently than larger or aggregated counterparts [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], a behavior consistent with the observed physicochemical properties of the dual-extract ZnO NPs. Additionally, the controlled release of Zn\u0026sup2;⁺ ions within the acidic intracellular or tumor-like microenvironment may further disrupt cellular metabolic pathways and enhance cytotoxic effects. Importantly, the phytochemical surface capping imparted by the green synthesis route may improve biocompatibility and reduce nonspecific toxicity toward normal cells, supporting safer anticancer applications. While the in vitro findings demonstrate promising ROS-mediated anticancer activity, further mechanistic studies and in vivo validation are required and constitute ongoing work.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003e5.2. Antidiabetic Potential\u003c/h2\u003e \u003cp\u003eZinc plays a critical role in insulin synthesis, storage, and secretion, and zinc deficiency is closely associated with insulin resistance and impaired glucose homeostasis [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The synthesized ZnO nanoparticles provide a highly bioavailable zinc source due to their small size and excellent dispersion stability, which may enhance cellular uptake and biological availability during in vitro antidiabetic evaluations. Mechanistically, ZnO nanoparticles may improve insulin signaling by interacting with insulin receptors and facilitating glucose uptake. Moreover, their antioxidant properties may mitigate oxidative stress associated with chronic hyperglycemia, thereby protecting pancreatic β-cells from oxidative damage and preserving insulin secretion capacity [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The stable phytochemical coating may also support controlled Zn\u0026sup2;⁺ release, reducing toxicity risks during cellular exposure. Collectively, these features highlight the potential of the synthesized ZnO nanoparticles as a multifunctional antidiabetic nanoplatform, warranting further in vitro and in vivo investigation.\u003c/p\u003e \u003c/div\u003e"},{"header":"6. Comparative Assessment with Reported Green Syntheses","content":"\u003cp\u003eA comparative evaluation with previously reported green synthesis routes was conducted to benchmark the performance of the present dual-extract system. As summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, ZnO nanoparticles synthesized using single-plant extracts typically exhibit broader particle size distributions (25\u0026ndash;60 nm) and moderate colloidal stability, with zeta potential values generally ranging from \u0026minus;\u0026thinsp;15 to \u0026minus;\u0026thinsp;22 mV. In contrast, the coriander\u0026ndash;orange dual-extract approach yielded smaller, monodisperse ZnO nanoparticles (24 nm) with a significantly higher negative zeta potential (\u0026minus;\u0026thinsp;28.6 mV), indicating superior dispersion stability. This improvement arises from the synergistic interaction between phenolic reducers and polymeric stabilizers, enabling decoupled control over nucleation and growth processes. Such enhanced size uniformity and stability are critical parameters for biomedical translation, as they directly influence cellular uptake, ROS generation, and reproducibility of in vitro responses. The comparative analysis clearly demonstrates that the dual-extract strategy offers a distinct and reproducible advantage over conventional single-extract green syntheses.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparative analysis of green-synthesized ZnO nanoparticles using various plant extracts\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlant Extract Source\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAverage Particle Size (nm)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eShape / Morphology\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eZeta Potential (mV)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDistinct Feature / Observation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eZiziphus\u003c/em\u003e leaf extract\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35\u0026ndash;50\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHexagonal / Irregular\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026minus;18.5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eModerate crystallinity; unstable dispersion\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAl-Assaly \u003cem\u003eet al.\u003c/em\u003e, 2024 [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eMangifera indica\u003c/em\u003e leaves\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28\u0026ndash;40\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNearly spherical\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026minus;20.1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGood yield; slight aggregation observed\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSharmila \u003cem\u003eet al.\u003c/em\u003e, 2015 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eParthenium hysterophorus\u003c/b\u003e \u003cb\u003eleaf\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e30\u0026ndash;45\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eMixed shapes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026minus;16.8\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eBroad size distribution; low stability\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eRajiv\u003c/b\u003e \u003cb\u003eet al.\u003c/b\u003e, \u003cb\u003e2013\u003c/b\u003e [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSeaweed\u003c/b\u003e \u003cb\u003eextract\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e25\u0026ndash;60\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eIrregular\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026minus;21.3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eLow reproducibility; limited control\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eNagarajan \u0026amp; Arumugam, 2013\u003c/b\u003e [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCoriandrum sativum\u003c/b\u003e \u003cb\u003e(coriander) extract\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e30\u0026ndash;42\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eQuasi-spherical\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026minus;20.2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eModerate uniformity; weak stability\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eSahib\u003c/b\u003e \u003cb\u003eet al.\u003c/b\u003e, \u003cb\u003e2013\u003c/b\u003e [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCitrus sinensis\u003c/b\u003e \u003cb\u003e(orange pith) extract\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e32\u0026ndash;48\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eIrregular spheres\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026minus;19.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eFlavonoid-rich capping; mild aggregation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eTripoli\u003c/b\u003e \u003cb\u003eet al.\u003c/b\u003e, \u003cb\u003e2007\u003c/b\u003e [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCoriander\u0026ndash;orange dual extract (present study)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e24 (18\u0026ndash;30)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eSpherical, monodisperse\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026minus;28.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eHigh stability, uniform size, synergistic capping\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eThis work\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"7. Conclusion and Future Perspectives","content":"\u003cp\u003eThe present study successfully demonstrates a novel, eco-friendly dual-extract strategy for the green synthesis of zinc oxide nanoparticles with enhanced size control and colloidal stability. The synergistic interaction between coriander stem and orange pith extracts enabled precise regulation of nanoparticle nucleation and growth, resulting in monodisperse ZnO nanoparticles with an average size of 24 nm and excellent dispersion stability. Comprehensive characterization confirmed the formation of highly crystalline wurtzite ZnO nanoparticles with persistent phytochemical surface capping, which plays a crucial role in preventing aggregation and ensuring stability under in vitro experimental conditions. Experimental validation of ROS generation further establishes a direct link between nanoparticle physicochemical properties and biological response. Beyond biomedical relevance, this work highlights the sustainable valorization of kitchen waste, aligning nanoparticle synthesis with circular economy principles. Future studies will focus on systematic biological evaluation, including in vitro cytotoxicity and enzyme inhibition assays, followed by in vivo validation and scale-up studies to facilitate translational applications. Overall, the proposed dual-extract approach provides a reproducible, scalable, and environmentally responsible platform for high-quality ZnO nanoparticle synthesis with demonstrated in vitro functional relevance.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study did not involve human participants or live animals. All experiments were conducted using plant materials and chemical reagents; therefore, ethical approval was not required.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and Materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this published article and its supplementary information. Additional data are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no external funding was received for this research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eP. Naveen\u003c/strong\u003e: Conceptualization, methodology, green synthesis of ZnO nanoparticles, experimental investigation, data acquisition, formal analysis, visualization, manuscript drafting, and revision.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Gopi Mamidi\u003c/strong\u003e: Supervision, validation of experimental design, interpretation of characterization data (XRD, FTIR, SEM/TEM, zeta potential), critical review of the manuscript, and academic guidance.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Indira Priyadarsini\u003c/strong\u003e: Plant material selection and authentication, phytochemical interpretation, support in green extraction strategy, mechanistic insight into phytochemical-mediated nanoparticle formation, and manuscript review.\u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors gratefully acknowledge Government Degree College (A), Nagari, for providing the necessary laboratory facilities and institutional support to carry out this research. The authors also thank the Department of Botany, Government Degree College (A), Nagari, for assistance with plant material authentication.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKołodziejczak-Radzimska, A. \u0026amp; Jesionowski, T. Z. Oxide\u0026mdash;From Synthesis to Application. \u003cem\u003eMaterials\u003c/em\u003e \u003cb\u003e7\u003c/b\u003e, 2833\u0026ndash;2881. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/ma7042833\u003c/span\u003e\u003cspan address=\"10.3390/ma7042833\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2014).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUmar, A. \u0026amp; Hahn, Y. Z. 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Size-Dependent Cytotoxicity of ZnO Nanoparticles. \u003cem\u003eJ. Biomed. Nanotechnol\u003c/em\u003e. \u003cb\u003e7\u003c/b\u003e, 95\u0026ndash;104 (2011).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEllen MacArthur Foundation.Towards the Circular Economy: Economic and Business Rationale for an Accelerated Transition, (2015).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Scheme 1","content":"\u003cp\u003eScheme 1 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Zinc oxide nanoparticles, dual-extract green synthesis, coriander stems, orange pith, phytochemical synergy, colloidal stability","lastPublishedDoi":"10.21203/rs.3.rs-8478181/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8478181/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eA sustainable dual-extract green synthesis of zinc oxide nanoparticles (ZnO NPs) is reported using \u003cem\u003eCoriandrum sativum\u003c/em\u003e stem extract and \u003cem\u003eCitrus sinensis\u003c/em\u003e pith extract\u0026mdash;two underutilized kitchen by-products. Unlike conventional chemical routes and single-extract green syntheses, this synergistic dual-extract approach exploits complementary phytochemicals to achieve enhanced control over nucleation, growth, and stabilization of ZnO nanoparticles. Zinc acetate was employed as the precursor under alkaline conditions, followed by controlled calcination to obtain highly crystalline ZnO NPs. Phenolics and terpenoids from coriander stems facilitated Zn\u0026sup2;⁺ reduction, while pectin and flavonoids from orange pith acted as efficient capping and stabilizing agents. Comprehensive characterization confirmed the formation of spherical, monodisperse ZnO NPs with an average size of 24 nm (XRD, TEM) and a sharp UV\u0026ndash;Vis absorption peak at 373 nm, corresponding to the wurtzite ZnO phase. FTIR analysis revealed persistent phytochemical functional groups (O\u0026ndash;H, C\u0026thinsp;=\u0026thinsp;O, C\u0026ndash;O\u0026ndash;C), confirming effective surface passivation, while zeta potential measurements (\u0026minus;\u0026thinsp;28.6 mV) demonstrated excellent colloidal stability. Comparative evaluation with reported green syntheses shows that the present dual-extract system yields smaller and more stable ZnO NPs than single-extract methods. The resulting physicochemical features\u0026mdash;uniform size, high surface area, and biocompatible surface chemistry\u0026mdash;render these ZnO NPs promising for biomedical applications, particularly anticancer and antidiabetic platforms. This work establishes a reproducible, scalable, and eco-friendly route for high-quality ZnO nanoparticle synthesis with translational potential.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e","manuscriptTitle":"Synergistic Dual-Extract Green Synthesis of Zinc Oxide Nanoparticles Using Coriander Stems and Orange Pith: Structural Characterization and In Vitro Biomedical Relevance ","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-07 16:05:16","doi":"10.21203/rs.3.rs-8478181/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"70d8a79a-6eea-4609-98bd-f61ebe43e2cc","owner":[],"postedDate":"January 7th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":60677159,"name":"Biological sciences/Biochemistry"},{"id":60677160,"name":"Biological sciences/Biotechnology"},{"id":60677161,"name":"Physical sciences/Chemistry"},{"id":60677162,"name":"Physical sciences/Materials science"},{"id":60677163,"name":"Physical sciences/Nanoscience and technology"}],"tags":[],"updatedAt":"2026-05-14T05:55:47+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-07 16:05:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8478181","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8478181","identity":"rs-8478181","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}