{"paper_id":"3d319bfc-b5a0-4510-8a7a-0bd197ec9abb","body_text":"Synthesis and characterization of superparamagnetic PEGylated zero valent iron gold (Fe0Au) nanoparticles | 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 Research Article Synthesis and characterization of superparamagnetic PEGylated zero valent iron gold (Fe0Au) nanoparticles María Ana Rivera Soto, Geonel Rodríguez Gattorno, Marco Antonio González López, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5397379/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 Iron-gold (Fe 0 -Au) nanoparticles are forefront agents in biomedicine because of their magnetic and plasmonic properties and are prime candidates for advanced biomedical applications such as magnetic hyperthermia, targeted drug delivery, and bioimaging. Synthesizing biocompatible, stable iron phase, and minimal borate-related cytotoxicity, Fe 0 -Au hybrid nanoparticles are a great challenge, This study presents an optimized, two-step synthetic approach to produce PEGylated Fe 0 -Au hybrid nanoparticles, employing NaBH 4 as a reducing agent under strictly anaerobic conditions. UV-Vis spectroscopy confirmed nanoparticle formation, with absorbance peaks at 260 nm for Fe 0 and 526 nm for Au, accompanied by discernible color shifts in the colloidal suspension, indicative of successful metal reduction. High Transmission electron microscopy (HRTEM) revealed a uniform spherical morphology with an average diameter of 50 nm, while X-ray photoelectron spectroscopy (XPS) demonstrated substantial minimization of borate byproducts, reducing these potentially cytotoxic residues to 14 atomic percent. Magnetization assessments showed hysteresis-free superparamagnetic behavior with a saturation magnetization of 75 Am²/kg for the PEGylated NPs, validating their suitability for precision hyperthermia and magnetic resonance imaging. These findings indicate that PEG functionalization enhances colloidal stability and effectively mitigates toxicity risks, rendering these Fe 0 -Au nanoparticles as highly viable candidates for preclinical and potentially translational biomedical applications. zero-valent iron gold nanoparticles polyethylenglicol magnetization hyperthermia Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Recently, hybrid metallic nanostructures have been extensively tested for biomedical applications including photothermal therapy, drug delivery, biosensing immunoassays, cellular labeling, and hyperthermia 1 – 4 . Knowing the properties of each compound in bimodal nanoparticle (NP) synthesis may enhance their ability to synthesize nanoparticles (NPs) for diverse uses. Iron NPs ranging from zero valent to the oxidized form of magnetite (Fe 3 O 4 ), maghemite (γ Fe 2 O 3 ), and hematite (Fe 2 O 3 ) have been at the forefront of hyperthermia, magnetic resonance, cell separation, detection research, and clinical trials for decades. The development of novel biocompatible nanomaterials with improved chemical and magnetic properties is a long-pursued goal 5 , 6 . The chemical synthesis of Fe 0 NPs in aqueous media poses a great challenge because of their high reactivity and easy oxidation in air or water, which could result in the formation of iron oxides and hydroxides, leading to the degradation of magnetic properties 7 , 8 . In iron NP synthesis, an air- or water-protective coating layer prevents iron oxidation. Gold (Au) is one of the most widely used coating materials for Fe NPs conferring core stabilization, maintaining magnetic properties (to a certain extent), and well-known surface chemistry 9 – 12 . In addition to their chemical properties, Au NPs are used in the biomedical field for biosensing, photoinduced therapy, cancer therapy, imaging, drug delivery, and radiosensitization of cell cancer via reactive oxygen species (ROS) production 13 , 14 . Iron-gold NPs can be synthesized and designed into various morphologies, including core-shell, dumbbell-shaped, heterodimer, hybrid, or heteronanocompound. Differences in morphologies and shapes (irregular and spherical) result in magnetic, optical, biocompatibility, and radiation-sensitizing effects 1 , 12 . The inclusion of capping agents improved NP dispersion, stability in the solution phase avoiding agglomeration, and prevented immunological and reticular endothelial system recognition. Depending on the NP surface and chemical affinity, many capping agents have been tarkisused, including, bovine serum albumin (BSA), Cetyltrimethylammonium bromide (CTAB), diethylenetriaminepentaacetic acid (DTPA), polyethylene glycol (PEG), and chitosan 11 , 15 – 17 . For biomedical applications, PEG is commonly used as a functionalizing agent in NPs because of its capacity to provide stealth and chemical affinity for a number of nanocompounds 18 – 20 . Owing to the complexity of iron-gold NPs synthesis, several synthetic procedures have been developed, including microemulsion, sonochemical, chemical vapor condensation, reverse micelles, thermal decomposition, and chemical reduction 21 – 24 . However, there is an accurate and easy method to reduce Fe salts (Fe (II) and Fe (III)) or Au salts (H 2 AuCl 4 3[H 2 O]) to Fe 0 and Au 021, 25 – 27 using a strong reductive agent such as NaBH 4 . Nevertheless, it has been reported that many reaction by-products, such as borates and borax 28 , where exposure to these compounds in a dose-dependent manner resulted in cytotoxicity and genotoxicity, could not be conveniently used for biomedical applications 29 – 31 . The main goal of this work is to propose a NaBH 4 reduction pathway to synthesize bimodal NPs of Fe 0 -Au functionalized with PEG-2SH, where boron by-products could be present in lower concentrations to minimize NP toxicity and obtain oxygen-free Fe 0 -Au NPs. Methods General reaction scheme suggested The synthesis of Fe 0 Au NPs was performed via a redox reaction through the oxidation of NaBH 4 as shown in the schematic Eq. 2 8,32 . In the formulation, we considered the formation of borate and tetraborate ions because both anions were detected by X-ray photoelectron spectroscopy (XPS) analysis. $$\\:{M}^{n+}+\\text{B}{H}_{4}^{-}\\to\\:{M}^{0}+{B}_{4}{O}_{7}^{2-}+{H}_{2}\\text{B}{O}_{3}$$ M n+ represents to iron and gold cations and their zero valent products. Synthesis of iron and gold reduced salts To determine the reduction of Fe and Au salts, we performed the reactions in a magnetic stirrer using the following salts: FeBr 2 1x10 − 3 M and H 2 AuCl 4 3 [H 2 O] 1x10 − 3 M, which were dissolved in water and reduced in an isopropanol/water (1/100) NaBH 4 (1x10 − 2 M M) solution. For the Uv-Vis characterization, we induced a reduction in FeBr 2 or H 2 AuCl 4 3[H 2 O]. The iron NPs were synthesized in a flask, where the iron solution was added. Once the Fe salt was dissolved, NaBH 4 solution was added dropwise to complete the Fe reduction. AuNP synthesis was performed using the same protocol as that used for Fe synthesis. To simultaneously reduce Fe and Au, the Fe solution was poured into the flask, and the Au solution was added afterward, allowing the solutions to mix perfectly, followed by the dropwise addition of the NaBH 4 solution. This step was immediately followed by optical absorption (Uv-Vis) spectroscopy. Synthesis of functionalized PEGylated FeAu NPs Reactions were performed in an anaerobic atmosphere (argon bubbling); deionized water was boiled for 30 min, and water, solvents, and isopropanol were purged by argon bubbling for 1 h. Before performing the reaction, we prepared different solutions: water/Au, water/PEG-2SH, and NaBH 4 isopropanol/water (1:100). concentrations of salts used in all reactions were FeBr 2 5x10 − 3 M, H 2 AuCl 4 3[H 2 O] 5x10 − 5 M, PEG-2SH 1% and NaBh 4 7.5x10 − 2 M. The reaction was performed in an ultrasonic bath to ensure complete dissolution of the salts. Once FeBr 2 was dissolved, half of the NaBH 4 solution was added at a constant flux of 1 ml/min for 5 min to allow iron reduction, and the gold solution was added immediately after the rest of the NaBH 4 was poured, allowing the NaBH 4 to reduce H 2 AuCl 4 3[H 2 O] for 10 min. To functionalize the NPs, we added a PEG solution as the final step, allowing them to mix for 10 min. The mixture was centrifuged at 4500 rpm for 40 min to collect the NPs. The aqueous phase was carefully removed in an anaerobic atmosphere, the solid phase was washed three times with isopropanol, and the NPs were dried under an argon flux. Characterization Uv-Vis spectra of the solutions and dispersions were measured with an Agilent 8453 G1103a spectrophotometer using an optical quartz cell with a volume of 1 mL. We proposed a modified synthesis pathway used in the Uv-Vis characterization for the synthesis of iron nude, iron gold, pegylated iron gold, and ascorbic acid iron-gold-NPs. X-ray diffraction analysis (XRD) was performed using an X-ray diffractometer (D8 Advance), XRD using a Bruker D8 Advance diffractometer with Cu-Ka radiation (1.54184 A), and a LynxEye detector operated in Bragg–Brentano geometry. All patterns of the samples were collected from 10° to 90°/(2h) with a step size of 0.025°. The surface composition of the NP’s was determined by X-ray photoelectron spectroscopy (XPS) (Thermoscientific k-alpha surface analysis) 8 scans, 1m, 4.4 s, 400 mM, CAE 50.0, 0.10 eV, Microscopy characterization was performed by FE-SEM AURIGA 3916 from ZEISS; the samples were observed at 10, 30, 50, and 100 × magnifications with an accelerating voltage of 2 kV. Equipped with an Energy Dispersive Spectrophotometer (EDS), the samples were observed at 10 ×, 30 ×, 50 ×, and 100 × magnifications with an accelerating voltage of 2 kV. The morphology of the NPs was characterized via High-Resolution Transmission Electron Microscopy (HRTEM) using a microscope JEM-ARM200F (Jeol) operating at 200 kV. Magnetic characterization was performed using a physical property measurement system (PPMS). A magnetic field was applied along the ribbon length (rolling direction) to minimize the internal demagnetizing magnetic field. The magnetic entropy change Δ S M as a function of temperature was calculated using Maxwell’s relation from a set of isothermal magnetization curves M (µ 0 H ). Results Characterization of Fe-Au reduced forms by Uv-Vis spectroscopy Our approach consisted of two steps. The first step was the reduction of FeBr 2 by the NaBH 4 solution for 5 min, and in the second step, a solution of H 2 AuCl 4 3 [H 2 O] was added to the solution obtained previously, after which a NaBH 4 solution was incorporated to induce Au reduction. Finally, a polyethylene glycol (PEG) solution was added to functionalize the Fe-Au-NPs. The oxidation of hydride ions to molecular hydrogen and the reduction of cations of Fe or Au are shown below in the general chemical equations 21 , 25 , 33 – 35 . $$\\:4F{e}_{aq}^{3+}+3\\text{B}{H}_{4}+9{H}_{2O}-\\to\\:4F{e}_{\\left(s\\right)}^{0}+3{H}_{2}B{O}_{3}++12{H}_{aq}^{+}+6{\\text{H}}_{2\\left(\\text{g}\\right)}$$ $$\\:HAuC{l}_{4}+4NaB{H}_{4}-\\to\\:A{u}^{0}+\\frac{5}{2}{H}_{2}+\\:2{B}_{2}{H}_{6}+4NaCl\\:$$ When the reduction of FeBr 2 or H 2 AuCl 4 3 [H 2 O] occurred, a change in color was observed. The colloid suspension turned dark, indicating FeBr 2 reduction, 30 or in the case of H 2 AuCl 4 3 [H 2 O] Au reduction, a yellowish solution turned red wine, which suggested the formation of NPs 36 , which occurred immediately after the addition of NaBH 4 . The synthesis of iron or gold NPs was corroborated by comparing the Uv-Vis spectra before and after the reduction of FeBr 2 and H 2 AuCl 4 3 [H 2 O] or the reduction of both salts at the same time (Fig. 1 ). The absorbance bands after FeBr 2 reduction appeared at 260 and 360 nm (Fig. 1 a) 30 . In the case of H 2 AuCl 4 3 [H 2 O] reduction, a noticeable band at 526 nm was observed (Fig. 1 b) 37 , 38 . The nanofluid resulting from consecutive reductions of FeBr 2 and H 2 AuCl 4 3 [H 2 O] presented peaks at 320 and 370 nm, representing the formation of Fe NPs. An absorbance band at 560 nm appears, confirming the reduction of the Au salts (Fig. 1 c). The absorbance bands confirmed the surface plasmon absorbance or size-dependent phenomenon due to the aggregation of Fe 0 Au NPs 30 , 39 , which suggested the synthesis of Fe 0 and AuNPs by NaBH 4 . In Fig. 1 shows the Uv-Vis electronic absorption spectra of FeBr 2 and H 2 AuCl 4 (tested separately) and in the mixture immediately after reduction with an excess of sodium borohydride. The Au-containing solution, which was initially pale yellow, changed to red wine after NaBH 4 addition, which is a clear indication of the formation of AuNPs. Note that AuNPs presented a spectrum that was dominated by light scattering over the entire wavelength range, clearly indicating the low stability of the gold colloid. However, a well-known surface plasmon resonance band was still observed (see the inset in Fig. 1 ), with a maximum at 526 nm. However, the color of the Fe colloid changed from brick red to dark black when NaBH 4 was added, and its Uv-Vis spectrum also showed a small contribution from light scattering. The Uv-Vis spectrum of Fe-Au-NPs showed an unexpected increase in the intensity of the surface plasmon band, suggesting an improvement in the gold colloid stability. The interactions of FeNPs with light acquire the collection of free electrons and produce surface plasmon resonance as Au falls in the visible and near-infrared regions, providing the properties of NPs for biomedical applications, such as photo-induced hyperthermia and photo-induced bioimaging 12 . To identify the presence of metallic Fe after the reduction process, the Fe NP sample was studied by XRD (Fig. S1 in Supporting Information). The XRD pattern suggests the presence of metallic iron with a body-centered cubic (BCC) crystal structure and its oxidized phase (S1a, b), lepidocrocite: FeO (OH) (JCPDS #044-4015) (S1c). The appearance of lepidocrocite in the sample was not surprising; it was one of the naturally occurring phases of iron oxyhydroxide resulting from the oxidation of iron zero-valent nanoparticles 40 . It will be shown hereafter, lepidocrocite appears to have dehydrated to produce hematite. Our aim was to synthesize PEGylated iron-gold nanoparticles for biomedical applications, which suggested the reduction of iron and gold salts to obtain iron-gold nanoparticles, whereas XRD suggested the presence of Fe 0 . Nevertheless, NaBH 4 reduction-based synthesis produced several by-products with concentrations as high as 20% in weight 41 , almost all derivatives formed borax (B 2 O 3, B 2 H 6 and H 2 BO 3, ) or solid products like Iron borure (Fe 2 B) conferred to the NPs certain toxicity 9 , 21 , 25 , 42 . At high concentrations, borax byproducts have been reported to exhibit high toxicity in murine models and cell cultures. Murine models exposed to borax by-products at concentrations between 50 and 100 mg/kg/day show infertility, teratogenesis, hematopoietic syndromes, and liver damage as coagulative necrosis. In cell cultures, a series of concentrations of 0.4, 0.8, and 1.6 mg/l induced cytotoxicity and structural chromosomal aberrations 43 . Our special interest was in obtaining a PEGylated compound with a low concentration of NaBH 4 by-products. To obtain a lower concentration of reaction by-products, we developed two different strategies: to work with the lowest NaBH 4 concentrations possible to achieve FeBr 2 and H 2 AuCl 4 3[H 2 O] reduction. Thus, we minimized the concentration of the borax by-products. In addition, we tried out several organic and inorganic compounds to wash the NPs after the synthesis (methanol, acetone, dimethylformamide ethanol, isopropanol, and 1:1 solution as toluene/methanol, acetone/methanol, chloroform/methanol, hexane/methanol, and isopropanol/water) (supplementary2 Fig. 2 )., supplementary2 Table 1). Using XPS spectroscopy (data not shown), we found that among all the above combinations, isopropanol/water was the best at lowering the B concentration (up to 14 atomic percentage) in our samples, which appeared to form part of the by-product chemical compounds, such as Na 2 B 4 O 2 and FeB, incorporated as solids in the NPs (supplementary2 Fig. 2 , supplementary 2 table1 9,21,25,44 Fe (0) nanoparticles are prone to oxidation, resulting in the formation of a thin, amorphous iron oxide layer. 45 However, the nanoparticles can be stabilized by chemical reduction to form a binary NP system (iron gold) covered by a polymeric inert layer that protects them from oxidation (PEG) 12 . PEGylated FeAu NPs characterization by XPS To gain an understanding of the difference between Fe and Au valence occurrences, as well as to assess the presence of by-products of NaBH 4 reduction reactions at the surface of the PEGylated Fe 0 Au NPs, we performed XPS, as shown in Fig. 2 . Even when performing all chemical reactions in an anaerobic atmosphere, the high oxygen affinity of Fe 0 NPs carried on an iron oxide layer. Using XPS spectroscopy, two phases of Fe NPs were determined: Fe 0 and Fe 2 O 3 (hematite) at 4.35 weight % and 27.67 weight %, respectively (Fig. 2 a, Table 1) 46 ]. Even an inert element such as Au (4.2 weight %, as Au 0 ) oxidizes at the nanometric scale, and a small amount of AuO was detected in our samples (Fig. 2 b, Table 1), because of NaBH 4 reduction 47 and ultrasonic treatment 7 . This analysis also revealed the presence of boron in the samples (Fig. 2 c, Table 1). The peak at 193.1 eV was related to Na–B bonds presented as borax (Na 2 B 4 O 2 ) and the other one observed at 187.7 eV was due to Fe–B bonds. Interestingly, in addition to the expected metallic gold (83.8 eV) peak, our measurements also recorded another peak at 87.8 eV related to Au-O with a small atomic percentage (Fig. 2 b). Two phases of iron were observed; Fe 0 (Fe 0 ), characterized by peaks at 707 eV and 720 eV and hematite (Fe 2 O 3 ) with peaks at 710.8 eV and 719.8 eV (Fig. 2 a, Table 1). Furthermore, the ratio of oxidized Fe to metallic Fe (Fe 2 O 3 :Fe 0 ) was close to 6:1. (Fig. 2 a, Table 1). Table 1 . XPS measured weight percentage of PEGylated Fe Au NPs Table. 1. XPS weight % determined in PEGylated Fe Au NPs synthesize by NaBH 4 . reduction in isopropanol /water solution. Panels represents: a. metallic iron, b. oxidated phase, c. gold, d. B-by-products Despite obtaining the amorphous phase of Fe 0 NPs by choosing a successive ultrasonic treatment method, it was possible to obtain binary NPs through core-shell morphology or heteronanocompounds. Part of this was because these processes contributed to heterogeneous nucleation owing to the nearby stabilized surface (developed by the first NP formation), where the second nucleation reaction (reduction of H 2 AuCl 4 3 [H 2 O]) occurred; nonetheless, there is a possibility of overlap in the growth processes. Using this approach, it is possible to obtain monodisperse NP size distributions 48 . Characterization by SEM and EDS We performed morphological and chemical studies of the PEGylated Fe 0 Au NPs by means of SEM (Figs. 3 a, b and c). A homogeneous spherical morphology was observed, where the agglomerate size ranged from 40 nm to 300 nm. At higher magnifications, the contrast differences suggest that agglomerates were formed by small NPs. According to EDS analysis (Fig. 3 d, e, and f), the Fe/Au ratio was approximately 40 wt. %; and lightweight boron was undetected. The SEM results showed monodisperse NPs with an average size of 50 nm (Fig. 3 ) and heteronanocompound morphology with a tendency to form chain agglomerates even in the presence of PEG. Fe 0 / Fe 2 O 3 -NPs and AuNPs were identified using a fast Fourier transform (FFT) in the HRTEM measurements (Fig. 4 a, b). NP proximity increases in colloidal suspensions, which raises magnetic attraction influencing the particles’ random walk, which is involved in its growth and chain agglomeration formation, due to thermodynamic instability caused by attractive or repulsive potential energies, such as steric effects, electrostatic forces, van der Waals forces, and translational diffusion movement 45 , 49 , 50 . In nude iron NPs (Fe 0, Fe 2 O 3 ), iron gold, and PEGylated NPs presented agglomerates and chain formation (Fig. 4 ). HRTEM Characterization From the microscopic characterization of PEGylated iron gold NPs we determined their average size, composition, and structure (Fig. 4 ). Single nanoparticles with sizes of 4 ± 2 nm tended to form agglomerates with sizes of 30 ± 12 nm. As shown in (Fig. 4 ), the NPs formed heteronanocompound structures. PEG-protected NPs showed a double-layer structure; the layer nearest to the core was characterized as an Au layer with a diameter of 2 ± 2 nm, whereas the external layer had a length of 4 ± 2 nm. In Fig. 4 a, a micrograph of PEGylated Fe 0 Au NPs is shown, which reveals that the sample is composed of a complex mixture of amorphous and nanocrystalline nanoparticles, which formed an agglomerate homogeneously protected by an amorphous shell with a thickness ranging from 3 to 4 nm, and the low contrast of the shell indicates that it corresponded to PEG molecules. Metallic iron and gold nanocrystals can be distinguished within the nanoparticles. The Fast Fourier Transform (FFT) of the selected areas allowed identification of the zone axis and d hkl of metallic iron and gold NPs crystallized in body-centered cubic (BCC) and face-centered cubic (FCC) crystal structures, respectively. It should be noted that it was quite difficult to differentiate iron and gold if both coincided in their zone axis < 001> (i.e., the observed pattern agrees with d hkl within the precision of the microscope). In general, it can be stated that samples of PEGylated iron gold NPs appear to be composed of a hetero-nanocomposite with metallic gold and iron placed in adjacent contacts, both covered by a shell of PEG. In addition, a high-angle annular dark-field (HAADF) image contrast, the sensitivity of which nearly depends on Z 2 , shows similar features (see Fig. 4 b). Despite the agglomerate formation and semi-crystalline morphology (Fig. 4 ), the NPs synthesized in this work displayed superparamagnetic behavior 51 – 53 owing to the absence of hysteresis in the magnetization curves (Fig. 5 ) as a superparamagnetic material. The values in the magnetization saturation of 150 Am 2 kg − 1 on Fe 0 and Fe 0 Au NPs are similar to that of Fe 3 O 4 , the main material used in magnetic hyperthermia. Functionalization with PEG considerably lowered the magnetization saturation value (up to 75 Am 2 kg − 1 ) (Fig. 5 ). The magnetic properties of NPs are influenced by many factors, such as quantum confinement of electrons (finite size), boundary between each particle, differences in chemical structure, oxidation, dangling bonds, the existence of surfactants, surface and shape effects, interparticle interactions, and stability over time. Spins increase while the particle size ratio surface decreases; this phenomenon gives surface spins greater importance. Decreasing the nanoparticle size leads them to become single domains and no longer sustain domain walls, granting them a great net magnetic potential owing to spin rotation 54 – 57 . The magnetic behavior could also be related to the presence of Fe 0 and Fe 2 O 3 in the NP (Fig. 5 a). The magnetic properties seem to be independent of the presence of Au (Fig. 5 b) 58 , but not in the case of PEG, where the saturation magnetization decreases from 150 Am 2 kg − 1 to 75 Am 2 kg − 1 in PEGylated Fe 0 AuNP (Fig. 5 c). This magnetic potential behavior could be due to the presence of diamagnetic PEG in PEGylated NPs 59 . Conclusions Nanomedicine is a relatively new discipline that involves the use of nanotechnology in biosensing, imaging, and treatment of diseases, such as cancer, arthritis, and diabetes, as nanocarriers to enhance conventional treatment or as therapy, such as photoinduced therapy and magnetic hyperthermia. We synthesized PEGylated hybrid Fe 0 Au nanoparticles using chemical ultrasonic treatment and chemical reduction. The synthesized PEGylated Fe 0 Au NPs could be used for hyperthermia treatment, magnetic drug targeting, and magnetic resonance imaging in biological models, as well as in humans, owing to their optical properties observed in the intensity of the surface plasmon band, low concentrations of borate by-products, and superparamagnetic behavior. Declarations Ethical Compliance : Our procedures did not involve human or animal assays, and there were no ethical issues in this article Acknowledgement We thank Dr. Daniel Bahena Uribe from CINVESTAV-IPN and Josue Romero Ibarra from the University Laboratory of Electronic Microscopy at UNAM for their technical support. Data Access Statement: All relevant data are within the paper and its Supporting Information files load. Author Contributions: MARS, GRG, and JJOT conceived of and designed the study. MARS performed the experiments. Analyzed the data: MARS, GRG, JJOT. GRG and JJOT contributed reagents/materials/analysis tools MARS, GRG, MAGL, EMGC, MBMB and JJOT wrote the manuscript. Funding information The analyses were carried out at the National Laboratory for Nano and Biomaterials, Cinvestav Mérida, financed by the FOMIX-Yucatán 2008–108160, CONACYT LAB-2009-01-123913, 292692, 294643, 188345, and 204822 Projects and CONACyT grant numbers SALUD-2012-01-18164 and UACM CCYT-CON-08. Conflict of interest The authors declare that they have no conflict of interest References Mohamadkazem M, Neshastehriz A, Amini SM, Moshiri A, Janzadeh A. Radiosensitising effect of iron oxide-gold nanocomplex for electron beam therapy of melanoma in vivo by magnetic targeting. IET Nanobiotechnol . 2023;17(3):212-223. doi:10.1049/nbt2.12129 Mujahid MH, Upadhyay TK, Khan F, et al. Metallic and metal oxide-derived nanohybrid as a tool for biomedical applications. 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Chem Commun (Camb) . 2014;50(91):14194-14196. doi:10.1039/c4cc05946h Jafari M, Rezvanpour A. Upconversion nano-particles from synthesis to cancer treatment: A review. Advanced Powder Technology . 2019;30(9):1731-1753. doi:10.1016/j.apt.2019.05.027 Klačanová K, Fodran P, Šimon P, et al. Formation of Fe ( 0 ) -Nanoparticles via Reduction of Fe ( II ) Compounds by Amino Acids and Their Subsequent Oxidation to Iron Oxides. 2013;2013(Ii). doi:10.1155/2013/961629 Liu A, Liu J, Zhang W xian. Transformation and composition evolution of nanoscale zero valent iron (nZVI) synthesized by borohydride reduction in static water. Chemosphere . 2015;119:1068-1074. doi:10.1016/j.chemosphere.2014.09.026 Glavee GN, Klabunde KJ, Sorensen CM, Hadjipanayis GC. Chemistry of borohydride reduction of iron(II) and iron(III) ions in aqueous and nonaqueous media. Formation of nanoscale Fe, FeB, and Fe2B powders. Inorg Chem . 1995;34(1):28-35. doi:10.1021/ic00105a009 Shen J, Li Z, Yan Q, Chen Y. Reactions of bivalent metal ions with borohydride in aqueous solution for the preparation of ultrafine amorphous alloy particles. J Phys Chem . Published online 1993:8504-8511. doi:10.1021/j100134a020 Yoon-Seok Chang, James T. Nurmi, Paul Tratnyek. Synthesis of Fe-nano Particles Obtained by Borohydride Reduction with Solvent. In: Battelle Press; 2008. Silva LIM, Pérez-Gramatges A, Larrude DG, Almeida JMS, Aucélio RQ, da Silva AR. Gold nanoparticles produced using NaBH4 in absence and in the presence of one-tail or two-tail cationic surfactants: Characteristics and optical responses induced by aminoglycosides. Colloids Surf A Physicochem Eng Asp . 2021;614. doi:10.1016/j.colsurfa.2021.126174 Ogarev VA, Rudoi VM, Dement’eva O V. Gold Nanoparticles: Synthesis, Optical Properties, and Application. Inorganic Materials: Applied Research . 2018;9(1):134-140. doi:10.1134/S2075113318010197 Salaheldin TA, Ali MA, Salah Eldin TA, Moghazy GM El, Tork IM, Omara II. Detection of E.coli O157:H7 in feed samples using gold nanoparticles sensor. IntJCurrMicrobiolAppSci . 2014;3(6):697-708. http://www.ijcmas.com Syahjoko Saputra I, Suhartati S, Yulizar Y. Synthesis and Characterization of Gold Nanoparticles (AuNPs) by Utilizing Bioactive Compound of Imperata Cylindrica (L.) Raeusch . Vol 22.; 2020. doi:10.14203/jkti.v22i1.448 Khajegi P, Rashidi-Huyeh M. Optical Properties of Gold Nanoparticles: Shape and Size Effects. International Journal of Optics and Photonics . 2021;15(1):41-48. doi:10.52547/ijop.15.1.41 Greenlee LF, Torrey JD, Amaro RL, Shaw JM. Kinetics of zero valent iron nanoparticle oxidation in oxygenated water. Environ Sci Technol . 2012;46(23):12913-12920. doi:10.1021/es303037k Gubin SP, Koksharov YA, Khomutov GB, Yurkov GY. Magnetic nanoparticles: Preparation, structure and properties. Usp Khim . 2005;74(6):539-574. doi:10.1070/rc2005v074n06abeh000897 Kamali M, Kamali AR. Preparation of borax pentahydrate from effluents of iron nanoparticles synthesis process. AIMS Energy . 2018;6(6):1067-1073. doi:10.3934/ENERGY.2018.6.1067 ATSDR. Toxicological Profile for Boron . 2007th ed. (Williams Malcolm, Mumtaz Moiz, Fay Mike, Scinicariello Franco, Jenkins Kim, eds.). Division of Toxicology and Environmental Medicine,; 2010. http://www.atsdr.cdc.gov/toxprofiles/tp26.pdf National Center for Biotechnology Information(2024). PubChem Compound Summary for CID 10219853 SBorateR. Sodium Borate. May 2024. https://pubchem.ncbi.nlm.nih.gov/compound/Sodium-Borate#section=Information-Sources Liu JP, Fullerton E, Gufleisch O, Sellmyer D. Nanoscale Magnetic Materials and Applications .; 2009. doi:10.1007/978-0-387-85600-1 Liu A, Liu J, Zhang W xian. Transformation and composition evolution of nanoscale zero valent iron (nZVI) synthesized by borohydride reduction in static water. Chemosphere . 2015;119(October 2014):1068-1074. doi:10.1016/j.chemosphere.2014.09.026 Prozorov R, Yeshurun Y, Prozorov T, Gedanken A. Magnetic irreversibility and relaxation in assembly of ferromagnetic nanoparticles. Phys Rev B . 1998;59(10):6956-6965. doi:10.1103/PhysRevB.59.6956 Bhosale MA, Chenna DR, Bhanage BM. Ultrasound Assisted Synthesis of Gold Nanoparticles as an Efficient Catalyst for Reduction of Various Nitro Compounds. ChemistrySelect . 2017;2(3):1225-1231. doi:10.1002/slct.201601851 Pana O, Teodorescu CM, Chauvet O, et al. Structure, morphology and magnetic properties of Fe-Au core-shell nanoparticles. Surf Sci . 2007;601(18):4352-4357. doi:10.1016/j.susc.2007.06.024 Nedylakova M, Medinger J, Mirabello G, Lattuada M. Iron oxide magnetic aggregates: Aspects of synthesis, computational approaches and applications. Adv Colloid Interface Sci . 2024;323. doi:10.1016/j.cis.2023.103056 De Biasi E, Zysler RD, Ramos CA, Romero H. Magnetization enhancement at low temperature due to surface ordering in Fe-Ni-B amorphous nanoparticles. Physica B Condens Matter . 2002;320(1-4):203-205. doi:10.1016/S0921-4526(02)00682-8 Abdel Aziz WN, Bumajdad A, Al Sagheer F, Madkour M. Selective synthesis and characterization of iron oxide nanoparticles via PVA/PVP polymer blend as structure-directing agent. Mater Chem Phys . 2020;249. doi:10.1016/j.matchemphys.2020.122927 Tyagi N, Gupta P, Khan Z, et al. Superparamagnetic Iron-Oxide Nanoparticles Synthesized via Green Chemistry for the Potential Treatment of Breast Cancer. Molecules . 2023;28(5). doi:10.3390/molecules28052343 Bedanta S, Kleemann W. Supermagnetism. J Phys D Appl Phys . 2009;42(1):013001. doi:10.1088/0022-3727/42/1/013001 Gubin SP. Introduction. In: Gubin SP, ed. Magnetic Nanoparticles . Wiley‐VCH Verlag. ; 2009:1-23. Issa B, Obaidat IM, Albiss BA, Haik Y. Magnetic nanoparticles: Surface effects and properties related to biomedicine applications. Int J Mol Sci . 2013;14(11):21266-21305. doi:10.3390/ijms141121266 Andrade RGD, Veloso SRS, Castanheira EMS. Shape anisotropic iron oxide-based magnetic nanoparticles: Synthesis and biomedical applications. Int J Mol Sci . 2020;21(7). doi:10.3390/ijms21072455 Mendez-Garza J, Wang B, Madeira A, Giorgio C Di, Bossis G. Synthesis and Surface Modification of Spindle-Type Magnetic Nanoparticles: Gold Coating and PEG Functionalization. J Biomater Nanobiotechnol . 2013;4(July):222-228. doi:10.4236/jbnb.2013.43027 Cheraghipour E, Tamaddon AM, Javadpour S, Bruce IJ. PEG conjugated citrate-capped magnetite nanoparticles for biomedical applications. J Magn Magn Mater . 2013;328:91-95. doi:10.1016/j.jmmm.2012.09.042 Additional Declarations No competing interests reported. Supplementary Files Supplementarymaterial.docx 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-5397379\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":386656754,\"identity\":\"62ba8cdc-f539-49fb-b0b9-5e3a1e403dff\",\"order_by\":0,\"name\":\"María Ana Rivera Soto\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Universidad Autónoma de la Ciudad de México\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"María\",\"middleName\":\"Ana Rivera\",\"lastName\":\"Soto\",\"suffix\":\"\"},{\"id\":386656755,\"identity\":\"d41bbed9-652f-4882-b8a4-031c8f91d072\",\"order_by\":1,\"name\":\"Geonel Rodríguez Gattorno\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Centro de Investigación y de Estudios Avanzados\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Geonel\",\"middleName\":\"Rodríguez\",\"lastName\":\"Gattorno\",\"suffix\":\"\"},{\"id\":386656757,\"identity\":\"a1cb77b1-3d0f-40c1-bddc-42e913a9d378\",\"order_by\":2,\"name\":\"Marco Antonio González López\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Universidad Autónoma Metropolitana\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Marco\",\"middleName\":\"Antonio González\",\"lastName\":\"López\",\"suffix\":\"\"},{\"id\":386656758,\"identity\":\"1d79be48-323b-4211-aad9-8a94e1f7ab1a\",\"order_by\":3,\"name\":\"Elena Marcia Gutiérrez Cárdenas\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Universidad Autónoma Metropolitana\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Elena\",\"middleName\":\"Marcia Gutiérrez\",\"lastName\":\"Cárdenas\",\"suffix\":\"\"},{\"id\":386656759,\"identity\":\"83d5e3dd-800a-4341-ae59-732640761b9d\",\"order_by\":4,\"name\":\"Maximo Berto Martinez Benitez\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Universidad Autónoma de la Ciudad de México\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Maximo\",\"middleName\":\"Berto Martinez\",\"lastName\":\"Benitez\",\"suffix\":\"\"},{\"id\":386656760,\"identity\":\"666ae0a8-88eb-4d95-bcdd-078e47df2c46\",\"order_by\":5,\"name\":\"José de Jesús Olivares Trejo\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+klEQVRIiWNgGAWjYDACdsYGONuAoQJEEALMUC08YC1niNICpUFaGBjbiNDCz8zcJvFzj429vfThAwUf5x2WN2dvPsDwo2IbTi2SzYxtkj3P0hJ7+NISDGduO2y4s+dYAmPPmds4tRgcZmw24DlwOIGHh8fAmHfbYcYNN3IMmBnb8Gsx/HPgvz0PD/8HY945h+2J0dL4mOfAAcYeHh4GY96Gw4kEtQD90vhY5kByYs8ZNgPDGcfSkzecOZZwEJ9f+NnbHxx8c8DOnr2H+ZnBhxpr2w3Hmw8++FGBWwsyYANGSTOYdYAo9UDA/ICBoY5YxaNgFIyCUTCCAABoTlcrxStzDgAAAABJRU5ErkJggg==\",\"orcid\":\"\",\"institution\":\"Universidad Autónoma de la Ciudad de México\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"José\",\"middleName\":\"de Jesús Olivares\",\"lastName\":\"Trejo\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2024-11-05 17:38:20\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-5397379/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-5397379/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":71690400,\"identity\":\"0517269f-5604-4b1e-9040-2398bc14b3b9\",\"added_by\":\"auto\",\"created_at\":\"2024-12-17 18:03:01\",\"extension\":\"jpg\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":58284,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eCharacterization of Fe-Au reduced forms by Uv-Vis spectroscopy. Panels represent spectra of the synthesis of Fe, Au, Fe-Au NPs by reduction of FeBr\\u003csub\\u003e2\\u003c/sub\\u003e or H\\u003csub\\u003e2\\u003c/sub\\u003eAuCl\\u003csub\\u003e4 \\u003c/sub\\u003e3 [H\\u003csub\\u003e2\\u003c/sub\\u003eO] by NaBh\\u003csub\\u003e4\\u003c/sub\\u003e, Panels; a. Uv-Vis spectra of Fe NPs using NaBh\\u003csub\\u003e4 \\u003c/sub\\u003e1X10\\u003csup\\u003e-2\\u003c/sup\\u003eM,\\u003c/p\\u003e\\n\\u003cp\\u003eb. Uv-Vis spectra of Au NPs using NaBh\\u003csub\\u003e4 \\u003c/sub\\u003e1X10\\u003csup\\u003e-2\\u003c/sup\\u003eM, c. Uv-Vis spectra of Fe-Au NPs using NaBh\\u003csub\\u003e4 \\u003c/sub\\u003e1X10\\u003csup\\u003e-2\\u003c/sup\\u003eM. Square represents magnification of Au Np at 526nm.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"1.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5397379/v1/7d94174be85275516399da34.jpg\"},{\"id\":71690399,\"identity\":\"44f9c66f-92ca-452c-a6e1-2eeb473944c7\",\"added_by\":\"auto\",\"created_at\":\"2024-12-17 18:03:01\",\"extension\":\"jpg\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":37955,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eXPS binding energies determined in PEGylated Fe Au NPs synthesize by NaBH\\u003csub\\u003e4\\u003c/sub\\u003e. reduction in isopropanol /water solution. Panels represent, a. Fe (metallic iron and oxidated phase), b. Au (metallic gold and oxidated phase), c.\\u0026nbsp; B-by-products representing borates and iron borure\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"2.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5397379/v1/84aa1f0f871d8e6b420723b8.jpg\"},{\"id\":71690404,\"identity\":\"ecb8a26f-8419-45b5-98d1-7bedc2ef95ce\",\"added_by\":\"auto\",\"created_at\":\"2024-12-17 18:03:02\",\"extension\":\"jpg\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":139441,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eSEM and EDS micrographs of PEGylated iron gold NPs obtained from FeBr\\u003csub\\u003e2 \\u003c/sub\\u003e5x10\\u003csup\\u003e-3\\u003c/sup\\u003eM, H\\u003csub\\u003e2\\u003c/sub\\u003eAuCl\\u003csub\\u003e4 \\u003c/sub\\u003e5x10\\u003csup\\u003e-5\\u003c/sup\\u003eM and NaBH\\u003csub\\u003e4 \\u003c/sub\\u003e7.5 x10 \\u003csup\\u003e-2\\u003c/sup\\u003eM in presence of PEG-2SH 1%. Panels a, b represents NPs synthesize in different magnification, c. NPs size was determined, and was observed agglomerates and single small NPs. The elemental composition of Fe NPs was studied using EDS. As can be seen from pael d, e, f. The predominant peaks were of iron (Fe), gold (Au), Carbon (C) and sodium (Na). The weight percent (wt %) of nanoparticles was measured to be 86.1% for Fe 7.96% for O and 2.845 for Au 1.85% for Na. The high Fe loading enables easy magnetic recovery of as-prepared.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"3.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5397379/v1/eda6f6b028f79bf1e6059e1e.jpg\"},{\"id\":71690401,\"identity\":\"d9df8317-e114-4afc-8ce1-f811db58b5ee\",\"added_by\":\"auto\",\"created_at\":\"2024-12-17 18:03:01\",\"extension\":\"jpg\",\"order_by\":4,\"title\":\"Figure 4\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":103391,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eHRTEM micrograph in PEGylated Fe Au NPs. The insets at right hand correspond to the FFT of the selected area in the image allowing to differentiate metallic iron and gold NPs. The highlighted area in blue (false color) shows the existence of amorphous shell probably corresponding to PEG molecules, b. HAADF image, false color based on contrast difference, yellow: Au NPs, blue: PEG gray area: Fe and brown: unidentified amorphous\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"4.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5397379/v1/719641617f60d2ab5e323529.jpg\"},{\"id\":71690402,\"identity\":\"9d1bf2ee-2ede-4eb0-b9f8-44d5553c441b\",\"added_by\":\"auto\",\"created_at\":\"2024-12-17 18:03:01\",\"extension\":\"jpg\",\"order_by\":5,\"title\":\"Figure 5\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":44915,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eMagnetic characterization performed by\\u0026nbsp; \\u003cstrong\\u003ePPMS®.\\u003c/strong\\u003e \\u0026nbsp;Hysteresis curve as result from measured at 300°K. Panels represents iron, iron gold, PEGylated iron gold NPs synthesize by by NaBH\\u003csub\\u003e4\\u003c/sub\\u003e. reduction in isopropanol /water solution\\u003c/p\\u003e\\n\\u003cp\\u003ea Hysteresis curve of Fe NPs\\u003c/p\\u003e\\n\\u003cp\\u003eb Hysteresis curve of Fe Au NPs\\u003c/p\\u003e\\n\\u003cp\\u003ec Hysteresis curve of PEGylated FeAu NPs\\u003c/p\\u003e\\n\\u003cp\\u003eSquare represents magnification of different NPs hysteresis curve\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"5.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5397379/v1/5bacd28fb8a91233e5495b5a.jpg\"},{\"id\":75284167,\"identity\":\"63f8618d-3295-4bd6-9388-6555cc783935\",\"added_by\":\"auto\",\"created_at\":\"2025-02-03 04:01:40\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":1154426,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5397379/v1/c4dee44b-6416-493e-b511-962579999753.pdf\"},{\"id\":71690403,\"identity\":\"1a4184bf-3e8e-4c68-a93a-851bc8075a76\",\"added_by\":\"auto\",\"created_at\":\"2024-12-17 18:03:01\",\"extension\":\"docx\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":152276,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"Supplementarymaterial.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5397379/v1/00eea4db7d1a688898467572.docx\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Synthesis and characterization of superparamagnetic PEGylated zero valent iron gold (Fe0Au) nanoparticles\",\"fulltext\":[{\"header\":\"Introduction\",\"content\":\"\\u003cp\\u003eRecently, hybrid metallic nanostructures have been extensively tested for biomedical applications including photothermal therapy, drug delivery, biosensing immunoassays, cellular labeling, and hyperthermia\\u003csup\\u003e\\u003cspan additionalcitationids=\\\"CR2 CR3\\\" citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e\\u003c/sup\\u003e. Knowing the properties of each compound in bimodal nanoparticle (NP) synthesis may enhance their ability to synthesize nanoparticles (NPs) for diverse uses.\\u003c/p\\u003e \\u003cp\\u003eIron NPs ranging from zero valent to the oxidized form of magnetite (Fe\\u003csub\\u003e3\\u003c/sub\\u003eO\\u003csub\\u003e4\\u003c/sub\\u003e), maghemite (γ Fe\\u003csub\\u003e2\\u003c/sub\\u003eO\\u003csub\\u003e3\\u003c/sub\\u003e), and hematite (Fe\\u003csub\\u003e2\\u003c/sub\\u003eO\\u003csub\\u003e3\\u003c/sub\\u003e) have been at the forefront of hyperthermia, magnetic resonance, cell separation, detection research, and clinical trials for decades. The development of novel biocompatible nanomaterials with improved chemical and magnetic properties is a long-pursued goal\\u003csup\\u003e\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e\\u003c/sup\\u003e. The chemical synthesis of Fe\\u003csup\\u003e0\\u003c/sup\\u003e NPs in aqueous media poses a great challenge because of their high reactivity and easy oxidation in air or water, which could result in the formation of iron oxides and hydroxides, leading to the degradation of magnetic properties\\u003csup\\u003e\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e\\u003c/sup\\u003e. In iron NP synthesis, an air- or water-protective coating layer prevents iron oxidation. Gold (Au) is one of the most widely used coating materials for Fe NPs conferring core stabilization, maintaining magnetic properties (to a certain extent), and well-known surface chemistry\\u003csup\\u003e\\u003cspan additionalcitationids=\\\"CR10 CR11\\\" citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e\\u003c/sup\\u003e. In addition to their chemical properties, Au NPs are used in the biomedical field for biosensing, photoinduced therapy, cancer therapy, imaging, drug delivery, and radiosensitization of cell cancer via reactive oxygen species (ROS) production\\u003csup\\u003e\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e\\u003c/sup\\u003e. Iron-gold NPs can be synthesized and designed into various morphologies, including core-shell, dumbbell-shaped, heterodimer, hybrid, or heteronanocompound. Differences in morphologies and shapes (irregular and spherical) result in magnetic, optical, biocompatibility, and radiation-sensitizing effects\\u003csup\\u003e\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e\\u003c/sup\\u003e. The inclusion of capping agents improved NP dispersion, stability in the solution phase avoiding agglomeration, and prevented immunological and reticular endothelial system recognition. Depending on the NP surface and chemical affinity, many capping agents have been tarkisused, including, bovine serum albumin (BSA), Cetyltrimethylammonium bromide (CTAB), diethylenetriaminepentaacetic acid (DTPA), polyethylene glycol (PEG), and chitosan\\u003csup\\u003e\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e,\\u003cspan additionalcitationids=\\\"CR16\\\" citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e\\u003c/sup\\u003e. For biomedical applications, PEG is commonly used as a functionalizing agent in NPs because of its capacity to provide stealth and chemical affinity for a number of nanocompounds\\u003csup\\u003e\\u003cspan additionalcitationids=\\\"CR19\\\" citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e\\u003c/sup\\u003e. Owing to the complexity of iron-gold NPs synthesis, several synthetic procedures have been developed, including microemulsion, sonochemical, chemical vapor condensation, reverse micelles, thermal decomposition, and chemical reduction\\u003csup\\u003e\\u003cspan additionalcitationids=\\\"CR22 CR23\\\" citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR24\\\" class=\\\"CitationRef\\\"\\u003e24\\u003c/span\\u003e\\u003c/sup\\u003e. However, there is an accurate and easy method to reduce Fe salts (Fe (II) and Fe (III)) or Au salts (H\\u003csub\\u003e2\\u003c/sub\\u003eAuCl\\u003csub\\u003e4\\u003c/sub\\u003e 3[H\\u003csub\\u003e2\\u003c/sub\\u003eO]) to Fe\\u003csup\\u003e0\\u003c/sup\\u003e and Au\\u003csup\\u003e021,\\u003cspan additionalcitationids=\\\"CR26\\\" citationid=\\\"CR25\\\" class=\\\"CitationRef\\\"\\u003e25\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR27\\\" class=\\\"CitationRef\\\"\\u003e27\\u003c/span\\u003e\\u003c/sup\\u003e using a strong reductive agent such as NaBH\\u003csub\\u003e4\\u003c/sub\\u003e. Nevertheless, it has been reported that many reaction by-products, such as borates and borax\\u003csup\\u003e\\u003cspan citationid=\\\"CR28\\\" class=\\\"CitationRef\\\"\\u003e28\\u003c/span\\u003e\\u003c/sup\\u003e, where exposure to these compounds in a dose-dependent manner resulted in cytotoxicity and genotoxicity, could not be conveniently used for biomedical applications\\u003csup\\u003e\\u003cspan additionalcitationids=\\\"CR30\\\" citationid=\\\"CR29\\\" class=\\\"CitationRef\\\"\\u003e29\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR31\\\" class=\\\"CitationRef\\\"\\u003e31\\u003c/span\\u003e\\u003c/sup\\u003e. The main goal of this work is to propose a NaBH\\u003csub\\u003e4\\u003c/sub\\u003e reduction pathway to synthesize bimodal NPs of Fe\\u003csup\\u003e0\\u003c/sup\\u003e-Au functionalized with PEG-2SH, where boron by-products could be present in lower concentrations to minimize NP toxicity and obtain oxygen-free Fe\\u003csup\\u003e0\\u003c/sup\\u003e-Au NPs.\\u003c/p\\u003e\"},{\"header\":\"Methods\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eGeneral reaction scheme suggested\\u003c/h2\\u003e \\u003cp\\u003eThe synthesis of Fe\\u003csup\\u003e0\\u003c/sup\\u003eAu NPs was performed via a redox reaction through the oxidation of NaBH\\u003csub\\u003e4\\u003c/sub\\u003e as shown in the schematic Eq.\\u0026nbsp;2\\u003csup\\u003e8,32\\u003c/sup\\u003e. In the formulation, we considered the formation of borate and tetraborate ions because both anions were detected by X-ray photoelectron spectroscopy (XPS) analysis.\\u003cdiv id=\\\"Equa\\\" class=\\\"Equation\\\"\\u003e\\u003cdiv format=\\\"TEX\\\" class=\\\"mathdisplay\\\" id=\\\"FileID_Equa\\\" name=\\\"EquationSource\\\"\\u003e\\n$$\\\\:{M}^{n+}+\\\\text{B}{H}_{4}^{-}\\\\to\\\\:{M}^{0}+{B}_{4}{O}_{7}^{2-}+{H}_{2}\\\\text{B}{O}_{3}$$\\u003c/div\\u003e\\u003c/div\\u003e\\u003c/p\\u003e \\u003cp\\u003eM\\u003csup\\u003en+\\u003c/sup\\u003e represents to iron and gold cations and their zero valent products.\\u003c/p\\u003e \\u003c/div\\u003e\\n\\u003ch3\\u003eSynthesis of iron and gold reduced salts\\u003c/h3\\u003e\\n\\u003cp\\u003eTo determine the reduction of Fe and Au salts, we performed the reactions in a magnetic stirrer using the following salts: FeBr\\u003csub\\u003e2\\u003c/sub\\u003e 1x10\\u003csup\\u003e\\u0026minus;\\u0026thinsp;3\\u003c/sup\\u003e M and H\\u003csub\\u003e2\\u003c/sub\\u003eAuCl\\u003csub\\u003e4\\u003c/sub\\u003e 3 [H\\u003csub\\u003e2\\u003c/sub\\u003eO] 1x10\\u003csup\\u003e\\u0026minus;\\u0026thinsp;3\\u003c/sup\\u003e M, which were dissolved in water and reduced in an isopropanol/water (1/100) NaBH\\u003csub\\u003e4\\u003c/sub\\u003e (1x10\\u003csup\\u003e\\u0026minus;\\u0026thinsp;2\\u003c/sup\\u003eM M) solution. For the Uv-Vis characterization, we induced a reduction in FeBr\\u003csub\\u003e2\\u003c/sub\\u003e or H\\u003csub\\u003e2\\u003c/sub\\u003eAuCl\\u003csub\\u003e4\\u003c/sub\\u003e 3[H\\u003csub\\u003e2\\u003c/sub\\u003eO]. The iron NPs were synthesized in a flask, where the iron solution was added. Once the Fe salt was dissolved, NaBH\\u003csub\\u003e4\\u003c/sub\\u003e solution was added dropwise to complete the Fe reduction. AuNP synthesis was performed using the same protocol as that used for Fe synthesis. To simultaneously reduce Fe and Au, the Fe solution was poured into the flask, and the Au solution was added afterward, allowing the solutions to mix perfectly, followed by the dropwise addition of the NaBH\\u003csub\\u003e4\\u003c/sub\\u003e solution. This step was immediately followed by optical absorption (Uv-Vis) spectroscopy.\\u003c/p\\u003e\\n\\u003ch3\\u003eSynthesis of functionalized PEGylated FeAu NPs\\u003c/h3\\u003e\\n\\u003cp\\u003eReactions were performed in an anaerobic atmosphere (argon bubbling); deionized water was boiled for 30 min, and water, solvents, and isopropanol were purged by argon bubbling for 1 h. Before performing the reaction, we prepared different solutions: water/Au, water/PEG-2SH, and NaBH\\u003csub\\u003e4\\u003c/sub\\u003e isopropanol/water (1:100). concentrations of salts used in all reactions were FeBr\\u003csub\\u003e2\\u003c/sub\\u003e 5x10\\u003csup\\u003e\\u0026minus;\\u0026thinsp;3\\u003c/sup\\u003eM, H\\u003csub\\u003e2\\u003c/sub\\u003eAuCl\\u003csub\\u003e4\\u003c/sub\\u003e 3[H\\u003csub\\u003e2\\u003c/sub\\u003eO] 5x10\\u003csup\\u003e\\u0026minus;\\u0026thinsp;5\\u003c/sup\\u003eM, PEG-2SH 1% and NaBh\\u003csub\\u003e4\\u003c/sub\\u003e 7.5x10\\u003csup\\u003e\\u0026minus;\\u0026thinsp;2\\u003c/sup\\u003eM.\\u003c/p\\u003e \\u003cp\\u003eThe reaction was performed in an ultrasonic bath to ensure complete dissolution of the salts. Once FeBr\\u003csub\\u003e2\\u003c/sub\\u003e was dissolved, half of the NaBH\\u003csub\\u003e4\\u003c/sub\\u003e solution was added at a constant flux of 1 ml/min for 5 min to allow iron reduction, and the gold solution was added immediately after the rest of the NaBH\\u003csub\\u003e4\\u003c/sub\\u003e was poured, allowing the NaBH\\u003csub\\u003e4\\u003c/sub\\u003e to reduce H\\u003csub\\u003e2\\u003c/sub\\u003eAuCl\\u003csub\\u003e4\\u003c/sub\\u003e 3[H\\u003csub\\u003e2\\u003c/sub\\u003eO] for 10 min. To functionalize the NPs, we added a PEG solution as the final step, allowing them to mix for 10 min. The mixture was centrifuged at 4500 rpm for 40 min to collect the NPs. The aqueous phase was carefully removed in an anaerobic atmosphere, the solid phase was washed three times with isopropanol, and the NPs were dried under an argon flux.\\u003c/p\\u003e\\n\\u003ch3\\u003eCharacterization\\u003c/h3\\u003e\\n\\u003cp\\u003eUv-Vis spectra of the solutions and dispersions were measured with an Agilent 8453 G1103a spectrophotometer using an optical quartz cell with a volume of 1 mL. We proposed a modified synthesis pathway used in the Uv-Vis characterization for the synthesis of iron nude, iron gold, pegylated iron gold, and ascorbic acid iron-gold-NPs. X-ray diffraction analysis (XRD) was performed using an X-ray diffractometer (D8 Advance), XRD using a Bruker D8 Advance diffractometer with Cu-Ka radiation (1.54184 A), and a LynxEye detector operated in Bragg\\u0026ndash;Brentano geometry. All patterns of the samples were collected from 10\\u0026deg; to 90\\u0026deg;/(2h) with a step size of 0.025\\u0026deg;. The surface composition of the NP\\u0026rsquo;s was determined by X-ray photoelectron spectroscopy (XPS) (Thermoscientific k-alpha surface analysis) 8 scans, 1m, 4.4 s, 400 mM, CAE 50.0, 0.10 eV, Microscopy characterization was performed by FE-SEM AURIGA 3916 from ZEISS; the samples were observed at 10, 30, 50, and 100 \\u0026times; magnifications with an accelerating voltage of 2 kV. Equipped with an Energy Dispersive Spectrophotometer (EDS), the samples were observed at 10 \\u0026times;, 30 \\u0026times;, 50 \\u0026times;, and 100 \\u0026times; magnifications with an accelerating voltage of 2 kV. The morphology of the NPs was characterized via High-Resolution Transmission Electron Microscopy (HRTEM) using a microscope JEM-ARM200F (Jeol) operating at 200 kV. Magnetic characterization was performed using a physical property measurement system (PPMS). A magnetic field was applied along the ribbon length (rolling direction) to minimize the internal demagnetizing magnetic field. The magnetic entropy change Δ\\u003cem\\u003eS\\u003c/em\\u003e \\u003csub\\u003eM\\u003c/sub\\u003e as a function of temperature was calculated using Maxwell\\u0026rsquo;s relation from a set of isothermal magnetization curves \\u003cem\\u003eM\\u003c/em\\u003e (\\u0026micro;\\u003csub\\u003e0\\u003c/sub\\u003e \\u003cem\\u003eH\\u003c/em\\u003e).\\u003c/p\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cdiv id=\\\"Sec8\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eCharacterization of Fe-Au reduced forms by Uv-Vis spectroscopy\\u003c/h2\\u003e \\u003cp\\u003eOur approach consisted of two steps. The first step was the reduction of FeBr\\u003csub\\u003e2\\u003c/sub\\u003e by the NaBH\\u003csub\\u003e4\\u003c/sub\\u003e solution for 5 min, and in the second step, a solution of H\\u003csub\\u003e2\\u003c/sub\\u003eAuCl\\u003csub\\u003e4\\u003c/sub\\u003e 3 [H\\u003csub\\u003e2\\u003c/sub\\u003eO] was added to the solution obtained previously, after which a NaBH\\u003csub\\u003e4\\u003c/sub\\u003e solution was incorporated to induce Au reduction. Finally, a polyethylene glycol (PEG) solution was added to functionalize the Fe-Au-NPs. The oxidation of hydride ions to molecular hydrogen and the reduction of cations of Fe or Au are shown below in the general chemical equations\\u003csup\\u003e\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR25\\\" class=\\\"CitationRef\\\"\\u003e25\\u003c/span\\u003e,\\u003cspan additionalcitationids=\\\"CR34\\\" citationid=\\\"CR33\\\" class=\\\"CitationRef\\\"\\u003e33\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR35\\\" class=\\\"CitationRef\\\"\\u003e35\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003cdiv id=\\\"Equb\\\" class=\\\"Equation\\\"\\u003e\\u003cdiv format=\\\"TEX\\\" class=\\\"mathdisplay\\\" id=\\\"FileID_Equb\\\" name=\\\"EquationSource\\\"\\u003e\\n$$\\\\:4F{e}_{aq}^{3+}+3\\\\text{B}{H}_{4}+9{H}_{2O}-\\\\to\\\\:4F{e}_{\\\\left(s\\\\right)}^{0}+3{H}_{2}B{O}_{3}++12{H}_{aq}^{+}+6{\\\\text{H}}_{2\\\\left(\\\\text{g}\\\\right)}$$\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Equc\\\" class=\\\"Equation\\\"\\u003e\\u003cdiv format=\\\"TEX\\\" class=\\\"mathdisplay\\\" id=\\\"FileID_Equc\\\" name=\\\"EquationSource\\\"\\u003e\\n$$\\\\:HAuC{l}_{4}+4NaB{H}_{4}-\\\\to\\\\:A{u}^{0}+\\\\frac{5}{2}{H}_{2}+\\\\:2{B}_{2}{H}_{6}+4NaCl\\\\:$$\\u003c/div\\u003e\\u003c/div\\u003e\\u003c/p\\u003e \\u003cp\\u003eWhen the reduction of FeBr\\u003csub\\u003e2\\u003c/sub\\u003e or H\\u003csub\\u003e2\\u003c/sub\\u003eAuCl\\u003csub\\u003e4\\u003c/sub\\u003e 3 [H\\u003csub\\u003e2\\u003c/sub\\u003eO] occurred, a change in color was observed. The colloid suspension turned dark, indicating FeBr\\u003csub\\u003e2\\u003c/sub\\u003e reduction, \\u003csup\\u003e\\u003cspan citationid=\\\"CR30\\\" class=\\\"CitationRef\\\"\\u003e30\\u003c/span\\u003e\\u003c/sup\\u003eor in the case of H\\u003csub\\u003e2\\u003c/sub\\u003eAuCl\\u003csub\\u003e4\\u003c/sub\\u003e 3 [H\\u003csub\\u003e2\\u003c/sub\\u003eO] Au reduction, a yellowish solution turned red wine, which suggested the formation of NPs\\u003csup\\u003e\\u003cspan citationid=\\\"CR36\\\" class=\\\"CitationRef\\\"\\u003e36\\u003c/span\\u003e\\u003c/sup\\u003e, which occurred immediately after the addition of NaBH\\u003csub\\u003e4\\u003c/sub\\u003e. The synthesis of iron or gold NPs was corroborated by comparing the Uv-Vis spectra before and after the reduction of FeBr\\u003csub\\u003e2\\u003c/sub\\u003e and H\\u003csub\\u003e2\\u003c/sub\\u003eAuCl\\u003csub\\u003e4\\u003c/sub\\u003e 3 [H\\u003csub\\u003e2\\u003c/sub\\u003eO] or the reduction of both salts at the same time (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003eThe absorbance bands after FeBr\\u003csub\\u003e2\\u003c/sub\\u003e reduction appeared at 260 and 360 nm (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003ea)\\u003csup\\u003e\\u003cspan citationid=\\\"CR30\\\" class=\\\"CitationRef\\\"\\u003e30\\u003c/span\\u003e\\u003c/sup\\u003e. In the case of H\\u003csub\\u003e2\\u003c/sub\\u003eAuCl\\u003csub\\u003e4\\u003c/sub\\u003e3 [H\\u003csub\\u003e2\\u003c/sub\\u003eO] reduction, a noticeable band at 526 nm was observed (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003eb)\\u003csup\\u003e\\u003cspan citationid=\\\"CR37\\\" class=\\\"CitationRef\\\"\\u003e37\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR38\\\" class=\\\"CitationRef\\\"\\u003e38\\u003c/span\\u003e\\u003c/sup\\u003e. The nanofluid resulting from consecutive reductions of FeBr\\u003csub\\u003e2\\u003c/sub\\u003e and H\\u003csub\\u003e2\\u003c/sub\\u003eAuCl\\u003csub\\u003e4\\u003c/sub\\u003e 3 [H\\u003csub\\u003e2\\u003c/sub\\u003eO] presented peaks at 320 and 370 nm, representing the formation of Fe NPs.\\u003c/p\\u003e \\u003cp\\u003eAn absorbance band at 560 nm appears, confirming the reduction of the Au salts (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003ec). The absorbance bands confirmed the surface plasmon absorbance or size-dependent phenomenon due to the aggregation of Fe\\u003csup\\u003e0\\u003c/sup\\u003eAu NPs\\u003csup\\u003e\\u003cspan citationid=\\\"CR30\\\" class=\\\"CitationRef\\\"\\u003e30\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR39\\\" class=\\\"CitationRef\\\"\\u003e39\\u003c/span\\u003e\\u003c/sup\\u003e, which suggested the synthesis of Fe\\u003csup\\u003e0\\u003c/sup\\u003e and AuNPs by NaBH\\u003csub\\u003e4\\u003c/sub\\u003e. In Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e shows the Uv-Vis electronic absorption spectra of FeBr\\u003csub\\u003e2\\u003c/sub\\u003e and H\\u003csub\\u003e2\\u003c/sub\\u003eAuCl\\u003csub\\u003e4\\u003c/sub\\u003e (tested separately) and in the mixture immediately after reduction with an excess of sodium borohydride. The Au-containing solution, which was initially pale yellow, changed to red wine after NaBH\\u003csub\\u003e4\\u003c/sub\\u003e addition, which is a clear indication of the formation of AuNPs. Note that AuNPs presented a spectrum that was dominated by light scattering over the entire wavelength range, clearly indicating the low stability of the gold colloid. However, a well-known surface plasmon resonance band was still observed (see the inset in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e), with a maximum at 526 nm. However, the color of the Fe colloid changed from brick red to dark black when NaBH\\u003csub\\u003e4\\u003c/sub\\u003e was added, and its Uv-Vis spectrum also showed a small contribution from light scattering. The Uv-Vis spectrum of Fe-Au-NPs showed an unexpected increase in the intensity of the surface plasmon band, suggesting an improvement in the gold colloid stability. The interactions of FeNPs with light acquire the collection of free electrons and produce surface plasmon resonance as Au falls in the visible and near-infrared regions, providing the properties of NPs for biomedical applications, such as photo-induced hyperthermia and photo-induced bioimaging\\u003csup\\u003e\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003eTo identify the presence of metallic Fe after the reduction process, the Fe NP sample was studied by XRD (Fig. S1 in Supporting Information). The XRD pattern suggests the presence of metallic iron with a body-centered cubic (BCC) crystal structure and its oxidized phase (S1a, b), lepidocrocite: FeO (OH) (JCPDS #044-4015) (S1c). The appearance of lepidocrocite in the sample was not surprising; it was one of the naturally occurring phases of iron oxyhydroxide resulting from the oxidation of iron zero-valent nanoparticles\\u003csup\\u003e\\u003cspan citationid=\\\"CR40\\\" class=\\\"CitationRef\\\"\\u003e40\\u003c/span\\u003e\\u003c/sup\\u003e. It will be shown hereafter, lepidocrocite appears to have dehydrated to produce hematite.\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003eOur aim was to synthesize PEGylated iron-gold nanoparticles for biomedical applications, which suggested the reduction of iron and gold salts to obtain iron-gold nanoparticles, whereas XRD suggested the presence of Fe\\u003csup\\u003e0\\u003c/sup\\u003e. Nevertheless, NaBH\\u003csub\\u003e4\\u003c/sub\\u003e reduction-based synthesis produced several by-products with concentrations as high as 20% in weight \\u003csup\\u003e\\u003cspan citationid=\\\"CR41\\\" class=\\\"CitationRef\\\"\\u003e41\\u003c/span\\u003e\\u003c/sup\\u003e, almost all derivatives formed borax (B\\u003csub\\u003e2\\u003c/sub\\u003eO\\u003csub\\u003e3,\\u003c/sub\\u003e B\\u003csub\\u003e2\\u003c/sub\\u003eH\\u003csub\\u003e6\\u003c/sub\\u003e and H\\u003csub\\u003e2\\u003c/sub\\u003eBO\\u003csub\\u003e3,\\u003c/sub\\u003e) or solid products like Iron borure (Fe\\u003csub\\u003e2\\u003c/sub\\u003eB) conferred to the NPs certain toxicity \\u003csup\\u003e\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR25\\\" class=\\\"CitationRef\\\"\\u003e25\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR42\\\" class=\\\"CitationRef\\\"\\u003e42\\u003c/span\\u003e\\u003c/sup\\u003e. At high concentrations, borax byproducts have been reported to exhibit high toxicity in murine models and cell cultures. Murine models exposed to borax by-products at concentrations between 50 and 100 mg/kg/day show infertility, teratogenesis, hematopoietic syndromes, and liver damage as coagulative necrosis. In cell cultures, a series of concentrations of 0.4, 0.8, and 1.6 mg/l induced cytotoxicity and structural chromosomal aberrations\\u003csup\\u003e\\u003cspan citationid=\\\"CR43\\\" class=\\\"CitationRef\\\"\\u003e43\\u003c/span\\u003e\\u003c/sup\\u003e. Our special interest was in obtaining a PEGylated compound with a low concentration of NaBH\\u003csub\\u003e4\\u003c/sub\\u003e by-products. To obtain a lower concentration of reaction by-products, we developed two different strategies: to work with the lowest NaBH\\u003csub\\u003e4\\u003c/sub\\u003e concentrations possible to achieve FeBr\\u003csub\\u003e2\\u003c/sub\\u003e and H\\u003csub\\u003e2\\u003c/sub\\u003eAuCl\\u003csub\\u003e4\\u003c/sub\\u003e 3[H\\u003csub\\u003e2\\u003c/sub\\u003eO] reduction. Thus, we minimized the concentration of the borax by-products. In addition, we tried out several organic and inorganic compounds to wash the NPs after the synthesis (methanol, acetone, dimethylformamide ethanol, isopropanol, and 1:1 solution as toluene/methanol, acetone/methanol, chloroform/methanol, hexane/methanol, and isopropanol/water) (supplementary2 Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig4\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e)., supplementary2 Table\\u0026nbsp;1). Using XPS spectroscopy (data not shown), we found that among all the above combinations, isopropanol/water was the best at lowering the B concentration (up to 14 atomic percentage) in our samples, which appeared to form part of the by-product chemical compounds, such as Na\\u003csub\\u003e2\\u003c/sub\\u003eB\\u003csub\\u003e4\\u003c/sub\\u003eO\\u003csub\\u003e2\\u003c/sub\\u003e and FeB, incorporated as solids in the NPs (supplementary2 Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig4\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e, supplementary 2 table1\\u003csup\\u003e9,21,25,44\\u003c/sup\\u003e\\u003c/p\\u003e \\u003cp\\u003eFe (0) nanoparticles are prone to oxidation, resulting in the formation of a thin, amorphous iron oxide layer.\\u003csup\\u003e\\u003cspan citationid=\\\"CR45\\\" class=\\\"CitationRef\\\"\\u003e45\\u003c/span\\u003e\\u003c/sup\\u003e However, the nanoparticles can be stabilized by chemical reduction to form a binary NP system (iron gold) covered by a polymeric inert layer that protects them from oxidation (PEG)\\u003csup\\u003e\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003c/div\\u003e\\n\\u003ch3\\u003ePEGylated FeAu NPs characterization by XPS\\u003c/h3\\u003e\\n\\u003cp\\u003eTo gain an understanding of the difference between Fe and Au valence occurrences, as well as to assess the presence of by-products of NaBH\\u003csub\\u003e4\\u003c/sub\\u003e reduction reactions at the surface of the PEGylated Fe\\u003csup\\u003e0\\u003c/sup\\u003eAu NPs, we performed XPS, as shown in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig4\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e. Even when performing all chemical reactions in an anaerobic atmosphere, the high oxygen affinity of Fe\\u003csup\\u003e0\\u003c/sup\\u003e NPs carried on an iron oxide layer. Using XPS spectroscopy, two phases of Fe NPs were determined: Fe\\u003csup\\u003e0\\u003c/sup\\u003e and Fe\\u003csub\\u003e2\\u003c/sub\\u003eO\\u003csub\\u003e3\\u003c/sub\\u003e (hematite) at 4.35 weight % and 27.67 weight %, respectively (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig4\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003ea, Table\\u0026nbsp;1) \\u003csup\\u003e\\u003cspan citationid=\\\"CR46\\\" class=\\\"CitationRef\\\"\\u003e46\\u003c/span\\u003e\\u003c/sup\\u003e]. Even an inert element such as Au (4.2 weight %, as Au\\u003csup\\u003e0\\u003c/sup\\u003e) oxidizes at the nanometric scale, and a small amount of AuO was detected in our samples (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig4\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003eb, Table\\u0026nbsp;1), because of NaBH\\u003csub\\u003e4\\u003c/sub\\u003e reduction\\u003csup\\u003e\\u003cspan citationid=\\\"CR47\\\" class=\\\"CitationRef\\\"\\u003e47\\u003c/span\\u003e\\u003c/sup\\u003e and ultrasonic treatment\\u003csup\\u003e\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003e This analysis also revealed the presence of boron in the samples (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig4\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003ec, Table\\u0026nbsp;1). The peak at 193.1 eV was related to Na\\u0026ndash;B bonds presented as borax (Na\\u003csub\\u003e2\\u003c/sub\\u003eB\\u003csub\\u003e4\\u003c/sub\\u003eO\\u003csub\\u003e2\\u003c/sub\\u003e) and the other one observed at 187.7 eV was due to Fe\\u0026ndash;B bonds. Interestingly, in addition to the expected metallic gold (83.8 eV) peak, our measurements also recorded another peak at 87.8 eV related to Au-O with a small atomic percentage (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig4\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003eb). Two phases of iron were observed; Fe\\u003csup\\u003e0\\u003c/sup\\u003e (Fe\\u003csup\\u003e0\\u003c/sup\\u003e), characterized by peaks at 707 eV and 720 eV and hematite (Fe\\u003csub\\u003e2\\u003c/sub\\u003eO\\u003csub\\u003e3\\u003c/sub\\u003e) with peaks at 710.8 eV and 719.8 eV (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig4\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003ea, Table\\u0026nbsp;1). Furthermore, the ratio of oxidized Fe to metallic Fe (Fe\\u003csub\\u003e2\\u003c/sub\\u003eO\\u003csub\\u003e3\\u003c/sub\\u003e:Fe\\u003csup\\u003e0\\u003c/sup\\u003e) was close to 6:1. (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig4\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003ea, Table\\u0026nbsp;1).\\u003c/p\\u003e \\u003cp\\u003e\\u003cstrong\\u003eTable 1\\u003c/strong\\u003e. XPS measured weight percentage of PEGylated Fe Au NPs\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cimg src=\\\"data:image/png;base64,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\\\" width=\\\"210\\\" height=\\\"178\\\"\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTable. 1.\\u003c/strong\\u003e\\u0026nbsp; \\u0026nbsp;XPS weight % determined in PEGylated Fe Au NPs synthesize by NaBH\\u003csub\\u003e4\\u003c/sub\\u003e. reduction in isopropanol /water solution. Panels represents: a. metallic iron, b. oxidated phase, c. gold, d. B-by-products \\u0026nbsp;\\u003c/p\\u003e\\u003cp\\u003eDespite obtaining the amorphous phase of Fe\\u003csup\\u003e0\\u003c/sup\\u003e NPs by choosing a successive ultrasonic treatment method, it was possible to obtain binary NPs through core-shell morphology or heteronanocompounds. Part of this was because these processes contributed to heterogeneous nucleation owing to the nearby stabilized surface (developed by the first NP formation), where the second nucleation reaction (reduction of H\\u003csub\\u003e2\\u003c/sub\\u003eAuCl\\u003csub\\u003e4\\u003c/sub\\u003e 3 [H\\u003csub\\u003e2\\u003c/sub\\u003eO]) occurred; nonetheless, there is a possibility of overlap in the growth processes. Using this approach, it is possible to obtain monodisperse NP size distributions \\u003csup\\u003e\\u003cspan citationid=\\\"CR48\\\" class=\\\"CitationRef\\\"\\u003e48\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e\\n\\u003ch3\\u003eCharacterization by SEM and EDS\\u003c/h3\\u003e\\n\\u003cp\\u003eWe performed morphological and chemical studies of the PEGylated Fe\\u003csup\\u003e0\\u003c/sup\\u003eAu NPs by means of SEM (Figs.\\u0026nbsp;\\u003cspan refid=\\\"Fig5\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003ea, b and c). A homogeneous spherical morphology was observed, where the agglomerate size ranged from 40 nm to 300 nm. At higher magnifications, the contrast differences suggest that agglomerates were formed by small NPs. According to EDS analysis (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig5\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003ed, e, and f), the Fe/Au ratio was approximately 40 wt. %; and lightweight boron was undetected. The SEM results showed monodisperse NPs with an average size of 50 nm (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig5\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e) and heteronanocompound morphology with a tendency to form chain agglomerates even in the presence of PEG. Fe\\u003csup\\u003e0\\u003c/sup\\u003e/ Fe\\u003csub\\u003e2\\u003c/sub\\u003eO\\u003csub\\u003e3\\u003c/sub\\u003e-NPs and AuNPs were identified using a fast Fourier transform (FFT) in the HRTEM measurements (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig6\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003ea, b). NP proximity increases in colloidal suspensions, which raises magnetic attraction influencing the particles\\u0026rsquo; random walk, which is involved in its growth and chain agglomeration formation, due to thermodynamic instability caused by attractive or repulsive potential energies, such as steric effects, electrostatic forces, van der Waals forces, and translational diffusion movement\\u003csup\\u003e\\u003cspan citationid=\\\"CR45\\\" class=\\\"CitationRef\\\"\\u003e45\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR49\\\" class=\\\"CitationRef\\\"\\u003e49\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR50\\\" class=\\\"CitationRef\\\"\\u003e50\\u003c/span\\u003e\\u003c/sup\\u003e. In nude iron NPs (Fe\\u003csup\\u003e0,\\u003c/sup\\u003e Fe\\u003csub\\u003e2\\u003c/sub\\u003eO\\u003csub\\u003e3\\u003c/sub\\u003e), iron gold, and PEGylated NPs presented agglomerates and chain formation (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig6\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cdiv id=\\\"Sec11\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eHRTEM Characterization\\u003c/h2\\u003e \\u003cp\\u003eFrom the microscopic characterization of PEGylated iron gold NPs we determined their average size, composition, and structure (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig6\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003e). Single nanoparticles with sizes of 4\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;2 nm tended to form agglomerates with sizes of 30\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;12 nm. As shown in (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig6\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003e), the NPs formed heteronanocompound structures. PEG-protected NPs showed a double-layer structure; the layer nearest to the core was characterized as an Au layer with a diameter of 2\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;2 nm, whereas the external layer had a length of 4\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;2 nm. In Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig6\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003ea, a micrograph of PEGylated Fe\\u003csup\\u003e0\\u003c/sup\\u003eAu NPs is shown, which reveals that the sample is composed of a complex mixture of amorphous and nanocrystalline nanoparticles, which formed an agglomerate homogeneously protected by an amorphous shell with a thickness ranging from 3 to 4 nm, and the low contrast of the shell indicates that it corresponded to PEG molecules. Metallic iron and gold nanocrystals can be distinguished within the nanoparticles. The Fast Fourier Transform (FFT) of the selected areas allowed identification of the zone axis and d\\u003csub\\u003e\\u003cem\\u003ehkl\\u003c/em\\u003e\\u003c/sub\\u003e of metallic iron and gold NPs crystallized in body-centered cubic (BCC) and face-centered cubic (FCC) crystal structures, respectively. It should be noted that it was quite difficult to differentiate iron and gold if both coincided in their zone axis\\u0026thinsp;\\u0026lt;\\u0026thinsp;001\\u0026gt; (i.e., the observed pattern agrees with d\\u003csub\\u003e\\u003cem\\u003ehkl\\u003c/em\\u003e\\u003c/sub\\u003e within the precision of the microscope). In general, it can be stated that samples of PEGylated iron gold NPs appear to be composed of a hetero-nanocomposite with metallic gold and iron placed in adjacent contacts, both covered by a shell of PEG. In addition, a high-angle annular dark-field (HAADF) image contrast, the sensitivity of which nearly depends on \\u003cem\\u003eZ\\u003c/em\\u003e\\u003csup\\u003e\\u003cem\\u003e\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e\\u003c/em\\u003e\\u003c/sup\\u003e, shows similar features (see Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig6\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003eb).\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003eDespite the agglomerate formation and semi-crystalline morphology (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig6\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003e), the NPs synthesized in this work displayed superparamagnetic behavior \\u003csup\\u003e\\u003cspan additionalcitationids=\\\"CR52\\\" citationid=\\\"CR51\\\" class=\\\"CitationRef\\\"\\u003e51\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR53\\\" class=\\\"CitationRef\\\"\\u003e53\\u003c/span\\u003e\\u003c/sup\\u003e owing to the absence of hysteresis in the magnetization curves (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig7\\\" class=\\\"InternalRef\\\"\\u003e5\\u003c/span\\u003e) as a superparamagnetic material. The values in the magnetization saturation of 150 Am\\u003csup\\u003e\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e\\u003c/sup\\u003e kg\\u003csup\\u003e\\u0026minus;\\u0026thinsp;1\\u003c/sup\\u003e on Fe\\u003csup\\u003e0\\u003c/sup\\u003e and Fe\\u003csup\\u003e0\\u003c/sup\\u003eAu NPs are similar to that of Fe\\u003csub\\u003e3\\u003c/sub\\u003eO\\u003csub\\u003e4\\u003c/sub\\u003e, the main material used in magnetic hyperthermia. Functionalization with PEG considerably lowered the magnetization saturation value (up to 75 Am\\u003csup\\u003e\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e\\u003c/sup\\u003e kg\\u003csup\\u003e\\u0026minus;\\u0026thinsp;1\\u003c/sup\\u003e) (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig7\\\" class=\\\"InternalRef\\\"\\u003e5\\u003c/span\\u003e). The magnetic properties of NPs are influenced by many factors, such as quantum confinement of electrons (finite size), boundary between each particle, differences in chemical structure, oxidation, dangling bonds, the existence of surfactants, surface and shape effects, interparticle interactions, and stability over time. Spins increase while the particle size ratio surface decreases; this phenomenon gives surface spins greater importance. Decreasing the nanoparticle size leads them to become single domains and no longer sustain domain walls, granting them a great net magnetic potential owing to spin rotation\\u003csup\\u003e\\u003cspan additionalcitationids=\\\"CR55 CR56\\\" citationid=\\\"CR54\\\" class=\\\"CitationRef\\\"\\u003e54\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR57\\\" class=\\\"CitationRef\\\"\\u003e57\\u003c/span\\u003e\\u003c/sup\\u003e. The magnetic behavior could also be related to the presence of Fe\\u003csup\\u003e0\\u003c/sup\\u003e and Fe\\u003csub\\u003e2\\u003c/sub\\u003eO\\u003csub\\u003e3\\u003c/sub\\u003e in the NP (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig7\\\" class=\\\"InternalRef\\\"\\u003e5\\u003c/span\\u003ea). The magnetic properties seem to be independent of the presence of Au (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig7\\\" class=\\\"InternalRef\\\"\\u003e5\\u003c/span\\u003eb)\\u003csup\\u003e\\u003cspan citationid=\\\"CR58\\\" class=\\\"CitationRef\\\"\\u003e58\\u003c/span\\u003e\\u003c/sup\\u003e, but not in the case of PEG, where the saturation magnetization decreases from 150 Am\\u003csup\\u003e\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e\\u003c/sup\\u003e kg\\u003csup\\u003e\\u0026minus;\\u0026thinsp;1\\u003c/sup\\u003e to 75 Am\\u003csup\\u003e\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e\\u003c/sup\\u003e kg\\u003csup\\u003e\\u0026minus;\\u0026thinsp;1\\u003c/sup\\u003e in PEGylated Fe\\u003csup\\u003e0\\u003c/sup\\u003eAuNP (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig7\\\" class=\\\"InternalRef\\\"\\u003e5\\u003c/span\\u003ec). This magnetic potential behavior could be due to the presence of diamagnetic PEG in PEGylated NPs\\u003csup\\u003e\\u003cspan citationid=\\\"CR59\\\" class=\\\"CitationRef\\\"\\u003e59\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Conclusions\",\"content\":\"\\u003cp\\u003eNanomedicine is a relatively new discipline that involves the use of nanotechnology in biosensing, imaging, and treatment of diseases, such as cancer, arthritis, and diabetes, as nanocarriers to enhance conventional treatment or as therapy, such as photoinduced therapy and magnetic hyperthermia. We synthesized PEGylated hybrid Fe\\u003csup\\u003e0\\u003c/sup\\u003eAu nanoparticles using chemical ultrasonic treatment and chemical reduction. The synthesized PEGylated Fe\\u003csup\\u003e0\\u003c/sup\\u003eAu NPs could be used for hyperthermia treatment, magnetic drug targeting, and magnetic resonance imaging in biological models, as well as in humans, owing to their optical properties observed in the intensity of the surface plasmon band, low concentrations of borate by-products, and superparamagnetic behavior.\\u003c/p\\u003e \"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eEthical Compliance\\u003c/strong\\u003e:\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eOur procedures did not involve human or animal assays, and there were no ethical issues in this article\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgement\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eWe thank Dr. Daniel Bahena Uribe\\u0026nbsp;from CINVESTAV-IPN and Josue Romero Ibarra from the University Laboratory of Electronic Microscopy at UNAM for their technical support.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eData Access Statement:\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAll relevant data are within the paper and its Supporting Information files load.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthor Contributions:\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eMARS, GRG, and JJOT conceived of and designed the study. MARS performed the experiments. Analyzed the data: MARS, GRG, JJOT. GRG and JJOT contributed reagents/materials/analysis tools MARS, GRG, MAGL, EMGC, MBMB and JJOT wrote the manuscript.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding information\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe analyses were carried out at the National Laboratory for Nano and Biomaterials, Cinvestav Mérida, financed by the FOMIX-Yucatán 2008–108160, CONACYT LAB-2009-01-123913, 292692, 294643, 188345, and 204822 Projects and CONACyT grant numbers SALUD-2012-01-18164 and UACM CCYT-CON-08.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConflict of interest\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors declare that they have no conflict of interest\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eMohamadkazem M, Neshastehriz A, Amini SM, Moshiri A, Janzadeh A. 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Shape anisotropic iron oxide-based magnetic nanoparticles: Synthesis and biomedical applications. \\u003cem\\u003eInt J Mol Sci\\u003c/em\\u003e. 2020;21(7). doi:10.3390/ijms21072455\\u003c/li\\u003e\\n\\u003cli\\u003eMendez-Garza J, Wang B, Madeira A, Giorgio C Di, Bossis G. Synthesis and Surface Modification of Spindle-Type Magnetic Nanoparticles: Gold Coating and PEG Functionalization. \\u003cem\\u003eJ Biomater Nanobiotechnol\\u003c/em\\u003e. 2013;4(July):222-228. doi:10.4236/jbnb.2013.43027\\u003c/li\\u003e\\n\\u003cli\\u003eCheraghipour E, Tamaddon AM, Javadpour S, Bruce IJ. PEG conjugated citrate-capped magnetite nanoparticles for biomedical applications. \\u003cem\\u003eJ Magn Magn Mater\\u003c/em\\u003e. 2013;328:91-95. doi:10.1016/j.jmmm.2012.09.042\\u003c/li\\u003e\\n\\u003c/ol\\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\":\"info@researchsquare.com\",\"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\":\"zero-valent iron, gold, nanoparticles, polyethylenglicol, magnetization, hyperthermia\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-5397379/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-5397379/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003eIron-gold (Fe\\u003csup\\u003e0\\u003c/sup\\u003e-Au) nanoparticles are forefront agents in biomedicine because of their magnetic and plasmonic properties and are prime candidates for advanced biomedical applications such as magnetic hyperthermia, targeted drug delivery, and bioimaging. Synthesizing biocompatible, stable iron phase, and minimal borate-related cytotoxicity, Fe\\u003csup\\u003e0\\u003c/sup\\u003e-Au hybrid nanoparticles are a great challenge,\\u003c/p\\u003e \\u003cp\\u003eThis study presents an optimized, two-step synthetic approach to produce PEGylated Fe\\u003csup\\u003e0\\u003c/sup\\u003e-Au hybrid nanoparticles, employing NaBH\\u003csub\\u003e4\\u003c/sub\\u003e as a reducing agent under strictly anaerobic conditions. UV-Vis spectroscopy confirmed nanoparticle formation, with absorbance peaks at 260 nm for Fe\\u003csup\\u003e0\\u003c/sup\\u003e and 526 nm for Au, accompanied by discernible color shifts in the colloidal suspension, indicative of successful metal reduction. High Transmission electron microscopy (HRTEM) revealed a uniform spherical morphology with an average diameter of 50 nm, while X-ray photoelectron spectroscopy (XPS) demonstrated substantial minimization of borate byproducts, reducing these potentially cytotoxic residues to 14 atomic percent.\\u003c/p\\u003e \\u003cp\\u003eMagnetization assessments showed hysteresis-free superparamagnetic behavior with a saturation magnetization of 75 Am\\u0026sup2;/kg for the PEGylated NPs, validating their suitability for precision hyperthermia and magnetic resonance imaging. These findings indicate that PEG functionalization enhances colloidal stability and effectively mitigates toxicity risks, rendering these Fe\\u003csup\\u003e0\\u003c/sup\\u003e-Au nanoparticles as highly viable candidates for preclinical and potentially translational biomedical applications.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Synthesis and characterization of superparamagnetic PEGylated zero valent iron gold (Fe0Au) nanoparticles\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2024-12-17 18:02:57\",\"doi\":\"10.21203/rs.3.rs-5397379/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"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\":\"76d7cfe6-7420-4308-bb89-a3f0fdcef141\",\"owner\":[],\"postedDate\":\"December 17th, 2024\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2025-02-03T03:53:30+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2024-12-17 18:02:57\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-5397379\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-5397379\",\"identity\":\"rs-5397379\",\"version\":[\"v1\"]},\"buildId\":\"qtupq5eGEP_6zYnWcrvyt\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}