Irradiation-Induced Facile Synthesis and Characterization of Red Blood Cell-Like Polystyrene Particles

Irradiation-Induced Facile Synthesis and Characterization of Red Blood Cell-Like Polystyrene Particles | 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 Irradiation-Induced Facile Synthesis and Characterization of Red Blood Cell-Like Polystyrene Particles Wenhui Fan, Shuya Zhang, Qingyi Ni, Yue Rong, Tianping Wang, Hanzhou Liu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7735322/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 This study developed a green γ-ray irradiation-assisted polymerization-self-assembly synergy strategy to fabricate red blood cell (RBC)-like morphology in an additive/template-free aqueous system at room temperature. By tuning the styrene/water mass ratio (2%–10%) and irradiation dose (5–100 kGy), we systematically elucidated the regulation mechanisms of microsphere morphology and size. Under optimized conditions (5 wt% styrene, 20 kGy), the microspheres exhibited typical RBC-like structures with an average diameter of 525 nm, hydroxyl-enriched surfaces, and internal hollow cavities. This approach eliminates the reliance on additives and templates in conventional processes. RBC-like polystyrene particles irradiation-assisted synthesis self-assembly green synthesis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction In recent years, polymeric particles with controllable morphology have emerged as a focal point in functional materials research due to their groundbreaking applications in drug delivery systems, biomimetic sensors, stimuli-responsive coatings, and anisotropic photonic crystals [ 1 – 4 ]. In particular, precise regulation of particle topology—such as hollow [ 5 ], hemispherical [ 6 ], cylindrical [ 7 ], raspberry-like [ 8 ], hamburger-like [ 9 ], and red blood cell (RBC)-mimetic structures [ 10 ]—endows materials with unique mechanical properties, surface activity, and biocompatibility, thereby expanding their application scope in nanomedicine and tissue engineering. Among these, RBC-mimetic polymeric particles demonstrate remarkable biomimetic advantages owing to their close resemblance to natural red blood cells in terms of microscale dimensions, biconcave disc morphology, and excellent deformability. On one hand, their rheological properties effectively prolong blood circulation half-life; on the other hand, their large specific surface area and modifiable surface provide an ideal platform for drug loading and targeted delivery[ 11 – 13 ]. Therefore, developing efficient and controllable synthetic strategies for RBC-mimetic polymeric particles holds significant scientific value and application potential. Currently, the fabrication of non-spherical polymeric particles primarily relies on microfluidic template methods [ 14 ], emulsion interfacial polymerization[ 15 ], and physical/chemical deformation of preformed particles [ 16 ]. While these methods enable the construction of specific morphologies, they generally suffer from process complexity and the necessity of introducing external additives such as crosslinkers or surfactants, which limit the biocompatibility and scalability of the final products. For instance, Koichiro et al.[ 17 ] employed a multi-step electrospraying technique to construct RBC-mimetic particles, requiring precise control over electric field parameters and polymer solution rheology. Similarly, Xie et al. [ 18 ] first synthesized monodisperse polystyrene spheres, followed by divinylbenzene crosslinking to achieve morphological reconstruction. These approaches are not only time- and energy-intensive but also risk residual crosslinker contamination, potentially compromising biomedical applicability. Therefore, the development of green, facile, and template/additive-free synthetic methods has become a critical challenge in this field. It is noteworthy that conventional self-assembly strategies face significant challenges in constructing microscale non-spherical particles, as rapid sedimentation often disrupts solvent evaporation-induced directional assembly processes. To address this technical bottleneck, Fan et al. [ 19 , 20 ] proposed a γ-ray irradiation-assisted radical polymerization-self-assembly synergistic strategy, which successfully produced monodisperse hollow polystyrene microspheres in an aqueous system at room temperature, without requiring any chemical additives. However, the precise control over particle morphology, particularly the ability to fine-tune structural features such as size and surface topology through adjustable experimental parameters, remains an unresolved challenge in irradiation-induced synthesis systems. This lack of a systematic morphological regulation strategy significantly hinders the on-demand fabrication of complex biomimetic particles, such as RBC-like structures, for specialized applications. Building upon this foundation, styrene was selected as the matrix material in this study owing to its excellent chemical stability, strong hydrophobicity, low adhesion tendency, and cost-effectiveness in production. Through systematic optimization of key parameters such as irradiation dose and monomer concentration, this study successfully achieved the controlled synthesis of RBC-like polystyrene particles. Experiment Materials Styrene (> 99.0%) was purchased from Sinopharm Chemical Reagent Co. Deionized water was purified by Direct Q5 pure water system. 60 Co γ-ray source: The activity of the source was 2.072×10¹⁵ Bq. Synthesis Mixtures of styrene and deionized water with different ratios were placed in specialized irradiation glass tubes. Nitrogen gas was purged through the tubes to remove oxygen, and then the glass tubes were sealed. These glass tubes were equipped with a straight gas inlet and a curved outlet, and the tube openings were sealed to enhance airtightness. A straight needle was inserted below the mixture, and the gas flow rate and purging duration were adjusted to ensure thorough purging and complete removal of oxygen. After deoxygenation treatment by purging with high-purity nitrogen gas (99.9% concentration) for 20 minutes, the sealed bottles were irradiated under a ⁶⁰Co-γ ray source (with a source activity of 2.072×10 15 Bq). Irradiation at different absorbed doses was performed at room temperature. Following irradiation, the samples were centrifuged at 10,000 rpm for 10 minutes, and the lower layer was removed to obtain uniform RBC-like polystyrene particles. The particles were then subjected to vacuum freeze-drying to obtain the final product. (Fig. 1 ) Sample characterization Transmission electron microscopy (TEM, Tecnai G2 Spirit BioTwin, USA) was employed to examine the particle microstructure. For TEM analysis, the centrifuged sample was carefully deposited onto a copper grid and allowed to dry under vacuum conditions prior to imaging. For scanning electron microscopy (SEM, S-4700 FE-SEM, Hitachi, Japan) observations, the RBC-like polystyrene particles were first vacuum-dried to obtain a powdered form. The powder was then mounted on double-sided conductive tape and sputter-coated with a thin gold layer (15 s coating time) to enhance surface conductivity and image quality. The colloidal properties of the particles were evaluated using a Zetasizer Nano ZS90 system (Malvern Instruments, UK). The RBC-like polystyrene particles were stably dispersed in deionized water for simultaneous measurement of particle size distribution and zeta potential. Fourier transform infrared spectroscopy (FT-IR, Thermo iS50, USA) was performed to analyze the chemical structure of the polystyrene hollow microspheres. The freeze-dried samples were measured in total reflection mode to ensure optimal signal quality. All spectroscopic measurements were conducted after the samples reached constant weight through complete freeze-drying. Results and Discussion Surface Chemical Characterization RBC-like polystyrene particles with uniform red blood cell morphology were successfully synthesized via γ-ray irradiation (dose: 20 kGy) in a styrene/deionized water system with a mass ratio of 5%. As shown in Fig. 2 (a) , the particles exhibit a characteristic biconcave disk-like structure, closely resembling the geometric features of natural red blood cells. Particle size distribution analysis (Fig. 2 (b) ) revealed that the particle diameters range from 300 to 900 nm, with an average diameter of approximately 525 nm. To investigate the chemical composition of RBC-like polystyrene particles, FT-IR was used to characterize the samples (Fig. 3 (c) ). As a control, pure polystyrene polymers were synthesized using the same method, except that no deionized water was added during the synthesis process. The results showed that the microspheres exhibited characteristic absorption peaks at 3000–3105 cm⁻¹ and 2930 − 2850 cm⁻¹, which were attributed to the symmetric stretching vibration of the benzene ring C - H bond and the stretching vibration of the alkyl C - H bond, respectively [ 21 , 22 ]. The peak at 3570 cm⁻¹ in the RBC microspheres was attributed to the hydroxyl O - H on the microsphere surface, which was not detected in the pure polystyrene (PS) control sample, indicating the presence of oxygen radicals on the RBC-like polystyrene particles surface [ 23 ]. XPS fine - spectrum analysis ( Figs. 2 (d, e)) provided direct evidence for the surface chemical state. The C1s spectrum could be deconvoluted into three components after peak fitting: binding energies of 291.6 eV, 286.4 eV, and 284.8 eV corresponded to the C = C bond in the benzene ring conjugated system, hydroxylated carbon (C - OH), and the C - C bond in the polystyrene backbone, respectively. The characteristic peak at 532.3 eV in the O1s spectrum further confirmed the presence of hydroxyl oxygen atoms [ 24 ]. In addition, combined with EDS elemental analysis ( Fig. 2 (f)) , the oxygen content detected by XPS on the microsphere surface was 1.48 wt%, significantly higher than the 0.63 wt% detected by EDS. This difference was due to the different detection depths of the two techniques: XPS (~ 10 nm) mainly reflects the surface chemical composition, while EDS (~ 1 µm) reflects the elemental information of the deeper bulk phase [ 25 ]. This indicated that the oxidizing groups on the RBC-like polystyrene particles surface showed a gradient distribution characteristic. That is, the higher oxygen content on the surface was due to the rich hydroxyl groups, and the hollow structure of the RBC microspheres led to a lower oxygen content in the internal cavity than that in the surface layer, indirectly confirming the hollow structure of the synthesized microspheres. Collectively, these multiscale characterizations confirm that γ-ray irradiation effectively produces biomimetic RBC-like polymer particles with oxygen-rich surfaces. Effect of Concentration and γ-Ray Dose on the Morphological Evolution of polystyrene particles To investigate the effect of concentration on the morphology of microspheres, we examined the formation mechanism of RBC-like polystyrene particles under different styrene/deionized water mass ratios (2%, 5%, and 10%) at a fixed irradiation dose of 20 kGy. As shown in Figs. 3 (a-1, b-1) , when the mass ratio was 2%, the resulting particles exhibited a multi-pitted surface structure with an average diameter of approximately 200 nm. This morphological feature is likely associated with the insufficient polymerization rate at low monomer concentrations: the restricted diffusion of styrene molecules results in localized polymerization heterogeneity, leading to interfacial tension instability and the formation of surface defects. When the mass ratio was increased to 5% ( Figs. 3 (a-2, b-2)) , the microspheres developed a characteristic biconcave disk-like morphology, with an average diameter of 550 nm ( Fig. 3 (c)) . This observation suggests that a moderate monomer concentration optimally balances the synergistic interaction between radical polymerization kinetics and the self-assembly process: sufficient styrene monomers provide the necessary precursors for polymer chain growth, while water-phase-mediated interfacial self-assembly drives the formation of a thermodynamically stable biomimetic topology. However, as the mass ratio increased to 10% (Figs. 3 (a-3, b-3) ), the average particle diameter decreased to 400 nm with a concomitant reduction in dispersion uniformity. This concentration-dependent size inversion phenomenon can be attributed to the Trommsdorff effect (auto-acceleration effect), wherein the rapid growth of polymer chains significantly increases system viscosity, hindering the ordered arrangement of molecular chains and ultimately resulting in smaller, more polydisperse particles [ 26 ]. Based on the optimized styrene/deionized water mass ratio (5%), we further investigated the influence of γ-ray absorbed dose (5–100 kGy) on the morphological and dimensional control of RBC-like polystyrene particles. As shown in Figs. 4 (a-1, b) , low-dose irradiation (5 kGy) resulted in the formation of submicron circular pores (average diameter: 190 nm) on the particle surface, which can be attributed to the insufficient radical concentration induced by low irradiation: the limited number of active species leads to the polymerization process remaining in the early nucleation stage, preventing the formation of a continuous and dense polymer shell. When the dose increased to 10 kGy (Figs. 4 (a-2, b) ), the particles gradually transitioned toward a spherical shape, accompanied by the formation of surface indentations. This transitional morphology indicates that a moderate increase in irradiation energy promotes radical chain growth reactions but has not yet reached the critical condition required to fully overcome interfacial tension anisotropy. At the optimized dose of 20 kGy (Figs. 4 (a-3, b) ), biconcave disk-like particles with an average diameter of 525 nm were obtained. However, excessive irradiation (≥ 30 kGy) triggered a pronounced size reduction effect: at 30 kGy, the particles transformed into uniform spheres (diameter: 295 nm), while further increasing the dose to 50 kGy and 100 kGy resulted in additional size shrinkage to 232 nm and 180 nm, respectively (Figs. 4 (a-4) to 4(a-6) , (b) ). In summary, within the dose range of 5–20 kGy, the morphological evolution follows a “porous → transitional → RBC-like” kinetic pathway. In contrast, at doses exceeding 20 kGy, the system enters an “over-irradiation zone”, leading to structural homogenization and size reduction. The variations in particle size and zeta potential with irradiation dose are shown in (Fig. 4 (b) ). In the low-dose region (5–20 kGy), the high absolute values of zeta-potential (-29.5 to -31.8 mV) indicate stable surface charge density and strong electrostatic repulsion between particles, resulting in excellent dispersion stability. The peak value (-31.8 mV) observed at 20 kGy corresponds to the optimal morphology (RBC-like polystyrene particles), where maximum surface hydroxyl group exposure achieves the highest charge density. In the high-dose region (≥ 30 kGy), the sharp decrease in absolute zeta potential values and deteriorated dispersion stability suggest that excessive irradiation causes polymer chain crosslinking or degradation, which masks hydroxyl groups[ 27 ]. Mechanism research The formation of microspheres follows an irradiation-assisted free radical polymerization–self-assembly (IFPS) dynamic model (Fig. 5 ). In the first stage, radical polymerization is initiated by γ-ray irradiation. Specifically, γ-ray irradiation of the aqueous phase generates hydroxyl radicals (·OH), which simultaneously act as initiators and terminators in styrene polymerization, producing two characteristic chain segments—single-terminal hydroxyl polystyrene chains (SHC) and double-terminal hydroxyl polystyrene chains (DHC) [ 19 ]. The ratio of SHC to DHC formation depends on both irradiation dose and monomer concentration (Fig. 6 ). At lower doses ( 20 kGy), the increased radical collision frequency favors DHC formation. Subsequently, in the second stage, interfacial self-assembly occurs. Here, SHC and DHC segments serve as amphiphilic emulsifiers, driving styrene droplets to form a water-in-oil-in-water (W/O/W) multiphase structure. Due to the asymmetrical structure of SHC chains, which are hydrophilic at only one end, interfacial curvature develops, resulting in surface indentations or pores. In contrast, DHC chains, having hydrophilic groups at both ends, symmetrically adsorb onto the oil-water interface, reducing curvature stress and promoting smoother surfaces. Polymerization and self-assembly proceed concurrently, ultimately forming stable RBC-like microspheres through chain crosslinking and solidification [ 28 ]. The morphology and size of microspheres are synergistically regulated by irradiation dose and monomer concentration. At low irradiation doses (< 20 kGy) or low monomer concentrations (< 5 wt%), interface stress instability dominated by SHC results in porous structures. Under optimized conditions (20 kGy, 5 wt%), increased DHC proportions facilitate precise formation of RBC-mimetic morphology. Excessive irradiation (> 30 kGy), however, leads to over-crosslinking of polymer chains, causing structural homogenization. Conclusion In this study, we proposed a facile, efficient, and green synthesis strategy utilizing γ-ray irradiation-assisted radical polymerization coupled with self-assembly reactions to fabricate RBC-like polystyrene particles at room temperature. By systematically optimizing key parameters such as styrene-to-deionized water mass ratio and irradiation dose, precise control over the morphology, size, and uniformity of the RBC-like polystyrene particles was achieved. Our results revealed that the absorbed radiation dose and styrene-to-water mass ratio significantly influence particle morphology and size. Specifically, increasing the irradiation dose generates higher concentrations of oxygen-containing radicals, thus accelerating the self-assembly process and altering particle morphology accordingly. Declarations Acknowledgements We appreciate the financial support from the National Natural Science Foundation of China (22276132, U24B20194, 22406135), Gusu Innovation and Entrepreneurship Leading Talent Program Project (ZXL2024403), the Postdoctoral Science Foundation of China (GZC 20231888, 2024M762296) and a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). Data availability All relevant data used to produce these results are included in the manuscript. Conflict of interest The authors declare no Conflict of interest. Authorship contribution statement † These authors contributed equally. Wenhui Fan † : design and operation of the experiments and data analysis. Shuya Zhang † : writing and revising the chapters of the article. 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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-7735322","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":530656529,"identity":"3719013f-1bde-4a65-9fe8-6c25125707e3","order_by":0,"name":"Wenhui Fan","email":"","orcid":"","institution":"Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, National Clinical Research Center for Oral Diseases, Shanghai Research Institute of 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12:05:28","extension":"xml","order_by":33,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":74979,"visible":true,"origin":"","legend":"","description":"","filename":"40efce458d944708ba0f4e456e3bd4be1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7735322/v1/b56016739ee98e039791431e.xml"},{"id":93771587,"identity":"ff99c30f-682d-42be-97eb-8d8efb6dc744","added_by":"auto","created_at":"2025-10-17 12:05:28","extension":"html","order_by":34,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":82616,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7735322/v1/46d09a8e72e1f023b6265cf6.html"},{"id":93771550,"identity":"8b42d178-199c-4dcf-b3a5-a49adc65783f","added_by":"auto","created_at":"2025-10-17 12:05:27","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":508361,"visible":true,"origin":"","legend":"\u003cp\u003eSchematic illustration of the synthesis process of RBC-like polystyrene particles.\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7735322/v1/9f5829d534447b62b4ec530b.jpg"},{"id":93771552,"identity":"b8c81388-592b-4046-a26f-1bdcf064b7f6","added_by":"auto","created_at":"2025-10-17 12:05:27","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2432390,"visible":true,"origin":"","legend":"\u003cp\u003e(a) TEM image of RBC-like polystyrene particles; (b) diameter distribution and zeta potential; (c) FT-IR spectra with red curve representing RBC-like polystyrene particles and black curve representing pure PS particles; XPS analysis of (d) C1s and (e) O1s spectra; (f) Oxygen content and C/O (atom/atom) of hollow microspheres by using XPS spectroscopy and SEM-EDS element analysis. The styrene/deionized water ratio was 5%, and the absorbed dose was 20 kGy.\u003c/p\u003e","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7735322/v1/5000388fbc641c628cef4efe.jpg"},{"id":93771555,"identity":"328ba395-e6fc-4925-ae31-79b261ac6af9","added_by":"auto","created_at":"2025-10-17 12:05:27","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":3480056,"visible":true,"origin":"","legend":"\u003cp\u003e(a) SEM images of microspheres formed at different styrene/deionized water concentrations; (b) TEM images; (c) particle size distribution.\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7735322/v1/90ca60597d72d895101f68aa.jpg"},{"id":93771551,"identity":"bc44cf9c-7de7-4fb5-97db-3113e73828af","added_by":"auto","created_at":"2025-10-17 12:05:27","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":2021302,"visible":true,"origin":"","legend":"\u003cp\u003e(a) SEM images of microspheres formed at different absorbed doses; (b) Variations of particle size and zeta potential with irradiation dose.\u003c/p\u003e","description":"","filename":"Fig4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7735322/v1/13d7146c3b068066b422f432.jpg"},{"id":93772645,"identity":"0d631fd1-a05a-4739-87e9-c278bd0da870","added_by":"auto","created_at":"2025-10-17 12:13:27","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":572607,"visible":true,"origin":"","legend":"\u003cp\u003eMechanism of IFPS.\u003c/p\u003e","description":"","filename":"Fig5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7735322/v1/75687cef574f79d10e1c41e6.jpg"},{"id":93771559,"identity":"4adc9096-23fa-4ac3-ba2a-b6624fdf9482","added_by":"auto","created_at":"2025-10-17 12:05:27","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":1132678,"visible":true,"origin":"","legend":"\u003cp\u003eFormation mechanism of RBC-like polystyrene particles synthesized at (a) different concentrations and (b) different irradiation doses. Process 1 represents \" Irradiation free radical addition and polymerization process,\" and Process 2 represents \" Irradiation-induced self-assembly and polymerization process.\"\u003c/p\u003e","description":"","filename":"Fig6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7735322/v1/a3d4217c0bdfac329339f102.jpg"},{"id":93776417,"identity":"336eaa62-72ab-4fef-b19e-0864136ff6a0","added_by":"auto","created_at":"2025-10-17 12:37:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":10684765,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7735322/v1/6e5d9361-a613-4565-876d-5ce24d524ea2.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Irradiation-Induced Facile Synthesis and Characterization of Red Blood Cell-Like Polystyrene Particles","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIn recent years, polymeric particles with controllable morphology have emerged as a focal point in functional materials research due to their groundbreaking applications in drug delivery systems, biomimetic sensors, stimuli-responsive coatings, and anisotropic photonic crystals [\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In particular, precise regulation of particle topology\u0026mdash;such as hollow [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], hemispherical [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], cylindrical [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], raspberry-like [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], hamburger-like [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], and red blood cell (RBC)-mimetic structures [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u0026mdash;endows materials with unique mechanical properties, surface activity, and biocompatibility, thereby expanding their application scope in nanomedicine and tissue engineering. Among these, RBC-mimetic polymeric particles demonstrate remarkable biomimetic advantages owing to their close resemblance to natural red blood cells in terms of microscale dimensions, biconcave disc morphology, and excellent deformability. On one hand, their rheological properties effectively prolong blood circulation half-life; on the other hand, their large specific surface area and modifiable surface provide an ideal platform for drug loading and targeted delivery[\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Therefore, developing efficient and controllable synthetic strategies for RBC-mimetic polymeric particles holds significant scientific value and application potential.\u003c/p\u003e\u003cp\u003eCurrently, the fabrication of non-spherical polymeric particles primarily relies on microfluidic template methods [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], emulsion interfacial polymerization[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], and physical/chemical deformation of preformed particles [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. While these methods enable the construction of specific morphologies, they generally suffer from process complexity and the necessity of introducing external additives such as crosslinkers or surfactants, which limit the biocompatibility and scalability of the final products. For instance, Koichiro et al.[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] employed a multi-step electrospraying technique to construct RBC-mimetic particles, requiring precise control over electric field parameters and polymer solution rheology. Similarly, Xie et al. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] first synthesized monodisperse polystyrene spheres, followed by divinylbenzene crosslinking to achieve morphological reconstruction. These approaches are not only time- and energy-intensive but also risk residual crosslinker contamination, potentially compromising biomedical applicability. Therefore, the development of green, facile, and template/additive-free synthetic methods has become a critical challenge in this field.\u003c/p\u003e\u003cp\u003eIt is noteworthy that conventional self-assembly strategies face significant challenges in constructing microscale non-spherical particles, as rapid sedimentation often disrupts solvent evaporation-induced directional assembly processes. To address this technical bottleneck, Fan et al. [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] proposed a γ-ray irradiation-assisted radical polymerization-self-assembly synergistic strategy, which successfully produced monodisperse hollow polystyrene microspheres in an aqueous system at room temperature, without requiring any chemical additives. However, the precise control over particle morphology, particularly the ability to fine-tune structural features such as size and surface topology through adjustable experimental parameters, remains an unresolved challenge in irradiation-induced synthesis systems. This lack of a systematic morphological regulation strategy significantly hinders the on-demand fabrication of complex biomimetic particles, such as RBC-like structures, for specialized applications. Building upon this foundation, styrene was selected as the matrix material in this study owing to its excellent chemical stability, strong hydrophobicity, low adhesion tendency, and cost-effectiveness in production. Through systematic optimization of key parameters such as irradiation dose and monomer concentration, this study successfully achieved the controlled synthesis of RBC-like polystyrene particles.\u003c/p\u003e"},{"header":"Experiment","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eMaterials\u003c/h2\u003e\u003cp\u003eStyrene (\u0026gt;\u0026thinsp;99.0%) was purchased from Sinopharm Chemical Reagent Co. Deionized water was purified by Direct Q5 pure water system. \u003csup\u003e60\u003c/sup\u003eCo γ-ray source: The activity of the source was 2.072\u0026times;10\u0026sup1;⁵ Bq.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eSynthesis\u003c/h3\u003e\n\u003cp\u003eMixtures of styrene and deionized water with different ratios were placed in specialized irradiation glass tubes. Nitrogen gas was purged through the tubes to remove oxygen, and then the glass tubes were sealed. These glass tubes were equipped with a straight gas inlet and a curved outlet, and the tube openings were sealed to enhance airtightness. A straight needle was inserted below the mixture, and the gas flow rate and purging duration were adjusted to ensure thorough purging and complete removal of oxygen.\u003c/p\u003e\u003cp\u003eAfter deoxygenation treatment by purging with high-purity nitrogen gas (99.9% concentration) for 20 minutes, the sealed bottles were irradiated under a ⁶⁰Co-γ ray source (with a source activity of 2.072\u0026times;10\u003csup\u003e15\u003c/sup\u003e Bq). Irradiation at different absorbed doses was performed at room temperature. Following irradiation, the samples were centrifuged at 10,000 rpm for 10 minutes, and the lower layer was removed to obtain uniform RBC-like polystyrene particles. The particles were then subjected to vacuum freeze-drying to obtain the final product. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\n\u003ch3\u003eSample characterization\u003c/h3\u003e\n\u003cp\u003eTransmission electron microscopy (TEM, Tecnai G2 Spirit BioTwin, USA) was employed to examine the particle microstructure. For TEM analysis, the centrifuged sample was carefully deposited onto a copper grid and allowed to dry under vacuum conditions prior to imaging. For scanning electron microscopy (SEM, S-4700 FE-SEM, Hitachi, Japan) observations, the RBC-like polystyrene particles were first vacuum-dried to obtain a powdered form. The powder was then mounted on double-sided conductive tape and sputter-coated with a thin gold layer (15 s coating time) to enhance surface conductivity and image quality. The colloidal properties of the particles were evaluated using a Zetasizer Nano ZS90 system (Malvern Instruments, UK). The RBC-like polystyrene particles were stably dispersed in deionized water for simultaneous measurement of particle size distribution and zeta potential. Fourier transform infrared spectroscopy (FT-IR, Thermo iS50, USA) was performed to analyze the chemical structure of the polystyrene hollow microspheres. The freeze-dried samples were measured in total reflection mode to ensure optimal signal quality. All spectroscopic measurements were conducted after the samples reached constant weight through complete freeze-drying.\u003c/p\u003e"},{"header":"Results and Discussion","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eSurface Chemical Characterization\u003c/h2\u003e\u003cp\u003eRBC-like polystyrene particles with uniform red blood cell morphology were successfully synthesized via γ-ray irradiation (dose: 20 kGy) in a styrene/deionized water system with a mass ratio of 5%. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e(a)\u003c/b\u003e, the particles exhibit a characteristic biconcave disk-like structure, closely resembling the geometric features of natural red blood cells. Particle size distribution analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e(b)\u003c/b\u003e) revealed that the particle diameters range from 300 to 900 nm, with an average diameter of approximately 525 nm.\u003c/p\u003e\u003cp\u003eTo investigate the chemical composition of RBC-like polystyrene particles, FT-IR was used to characterize the samples (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e(c)\u003c/b\u003e). As a control, pure polystyrene polymers were synthesized using the same method, except that no deionized water was added during the synthesis process. The results showed that the microspheres exhibited characteristic absorption peaks at 3000\u0026ndash;3105 cm⁻\u0026sup1; and 2930\u0026thinsp;\u0026minus;\u0026thinsp;2850 cm⁻\u0026sup1;, which were attributed to the symmetric stretching vibration of the benzene ring C - H bond and the stretching vibration of the alkyl C - H bond, respectively [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The peak at 3570 cm⁻\u0026sup1; in the RBC microspheres was attributed to the hydroxyl O - H on the microsphere surface, which was not detected in the pure polystyrene (PS) control sample, indicating the presence of oxygen radicals on the RBC-like polystyrene particles surface [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. XPS fine - spectrum analysis \u003cb\u003e(\u003c/b\u003eFigs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e(d, e))\u003c/b\u003e provided direct evidence for the surface chemical state. The C1s spectrum could be deconvoluted into three components after peak fitting: binding energies of 291.6 eV, 286.4 eV, and 284.8 eV corresponded to the C\u0026thinsp;=\u0026thinsp;C bond in the benzene ring conjugated system, hydroxylated carbon (C - OH), and the C - C bond in the polystyrene backbone, respectively. The characteristic peak at 532.3 eV in the O1s spectrum further confirmed the presence of hydroxyl oxygen atoms [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn addition, combined with EDS elemental analysis \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e(f))\u003c/b\u003e, the oxygen content detected by XPS on the microsphere surface was 1.48 wt%, significantly higher than the 0.63 wt% detected by EDS. This difference was due to the different detection depths of the two techniques: XPS (~\u0026thinsp;10 nm) mainly reflects the surface chemical composition, while EDS (~\u0026thinsp;1 \u0026micro;m) reflects the elemental information of the deeper bulk phase [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. This indicated that the oxidizing groups on the RBC-like polystyrene particles surface showed a gradient distribution characteristic. That is, the higher oxygen content on the surface was due to the rich hydroxyl groups, and the hollow structure of the RBC microspheres led to a lower oxygen content in the internal cavity than that in the surface layer, indirectly confirming the hollow structure of the synthesized microspheres. Collectively, these multiscale characterizations confirm that γ-ray irradiation effectively produces biomimetic RBC-like polymer particles with oxygen-rich surfaces.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eEffect of Concentration and γ-Ray Dose on the Morphological Evolution of polystyrene particles\u003c/h2\u003e\u003cp\u003eTo investigate the effect of concentration on the morphology of microspheres, we examined the formation mechanism of RBC-like polystyrene particles under different styrene/deionized water mass ratios (2%, 5%, and 10%) at a fixed irradiation dose of 20 kGy. As shown in Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e(a-1, b-1)\u003c/b\u003e, when the mass ratio was 2%, the resulting particles exhibited a multi-pitted surface structure with an average diameter of approximately 200 nm. This morphological feature is likely associated with the insufficient polymerization rate at low monomer concentrations: the restricted diffusion of styrene molecules results in localized polymerization heterogeneity, leading to interfacial tension instability and the formation of surface defects.\u003c/p\u003e\u003cp\u003eWhen the mass ratio was increased to 5% \u003cb\u003e(\u003c/b\u003eFigs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e(a-2, b-2))\u003c/b\u003e, the microspheres developed a characteristic biconcave disk-like morphology, with an average diameter of 550 nm \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e(c))\u003c/b\u003e. This observation suggests that a moderate monomer concentration optimally balances the synergistic interaction between radical polymerization kinetics and the self-assembly process: sufficient styrene monomers provide the necessary precursors for polymer chain growth, while water-phase-mediated interfacial self-assembly drives the formation of a thermodynamically stable biomimetic topology. However, as the mass ratio increased to 10% (Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e(a-3, b-3)\u003c/b\u003e), the average particle diameter decreased to 400 nm with a concomitant reduction in dispersion uniformity. This concentration-dependent size inversion phenomenon can be attributed to the Trommsdorff effect (auto-acceleration effect), wherein the rapid growth of polymer chains significantly increases system viscosity, hindering the ordered arrangement of molecular chains and ultimately resulting in smaller, more polydisperse particles [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eBased on the optimized styrene/deionized water mass ratio (5%), we further investigated the influence of γ-ray absorbed dose (5\u0026ndash;100 kGy) on the morphological and dimensional control of RBC-like polystyrene particles. As shown in Figs.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e\u003cb\u003e(a-1, b)\u003c/b\u003e, low-dose irradiation (5 kGy) resulted in the formation of submicron circular pores (average diameter: 190 nm) on the particle surface, which can be attributed to the insufficient radical concentration induced by low irradiation: the limited number of active species leads to the polymerization process remaining in the early nucleation stage, preventing the formation of a continuous and dense polymer shell. When the dose increased to 10 kGy (Figs.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e\u003cb\u003e(a-2, b)\u003c/b\u003e), the particles gradually transitioned toward a spherical shape, accompanied by the formation of surface indentations. This transitional morphology indicates that a moderate increase in irradiation energy promotes radical chain growth reactions but has not yet reached the critical condition required to fully overcome interfacial tension anisotropy. At the optimized dose of 20 kGy (Figs.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e\u003cb\u003e(a-3, b)\u003c/b\u003e), biconcave disk-like particles with an average diameter of 525 nm were obtained. However, excessive irradiation (\u0026ge;\u0026thinsp;30 kGy) triggered a pronounced size reduction effect: at 30 kGy, the particles transformed into uniform spheres (diameter: 295 nm), while further increasing the dose to 50 kGy and 100 kGy resulted in additional size shrinkage to 232 nm and 180 nm, respectively (Figs.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e\u003cb\u003e(a-4) to 4(a-6)\u003c/b\u003e, \u003cb\u003e(b)\u003c/b\u003e). In summary, within the dose range of 5\u0026ndash;20 kGy, the morphological evolution follows a \u0026ldquo;porous \u0026rarr; transitional \u0026rarr; RBC-like\u0026rdquo; kinetic pathway. In contrast, at doses exceeding 20 kGy, the system enters an \u0026ldquo;over-irradiation zone\u0026rdquo;, leading to structural homogenization and size reduction.\u003c/p\u003e\u003cp\u003eThe variations in particle size and zeta potential with irradiation dose are shown in (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e\u003cb\u003e(b)\u003c/b\u003e). In the low-dose region (5\u0026ndash;20 kGy), the high absolute values of zeta-potential (-29.5 to -31.8 mV) indicate stable surface charge density and strong electrostatic repulsion between particles, resulting in excellent dispersion stability. The peak value (-31.8 mV) observed at 20 kGy corresponds to the optimal morphology (RBC-like polystyrene particles), where maximum surface hydroxyl group exposure achieves the highest charge density. In the high-dose region (\u0026ge;\u0026thinsp;30 kGy), the sharp decrease in absolute zeta potential values and deteriorated dispersion stability suggest that excessive irradiation causes polymer chain crosslinking or degradation, which masks hydroxyl groups[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eMechanism research\u003c/h3\u003e\n\u003cp\u003eThe formation of microspheres follows an irradiation-assisted free radical polymerization\u0026ndash;self-assembly (IFPS) dynamic model (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). In the first stage, radical polymerization is initiated by γ-ray irradiation. Specifically, γ-ray irradiation of the aqueous phase generates hydroxyl radicals (\u0026middot;OH), which simultaneously act as initiators and terminators in styrene polymerization, producing two characteristic chain segments\u0026mdash;single-terminal hydroxyl polystyrene chains (SHC) and double-terminal hydroxyl polystyrene chains (DHC) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe ratio of SHC to DHC formation depends on both irradiation dose and monomer concentration (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). At lower doses (\u0026lt;\u0026thinsp;20 kGy), the limited radical density preferentially produces SHC chains, whereas at higher doses (\u0026gt;\u0026thinsp;20 kGy), the increased radical collision frequency favors DHC formation. Subsequently, in the second stage, interfacial self-assembly occurs. Here, SHC and DHC segments serve as amphiphilic emulsifiers, driving styrene droplets to form a water-in-oil-in-water (W/O/W) multiphase structure. Due to the asymmetrical structure of SHC chains, which are hydrophilic at only one end, interfacial curvature develops, resulting in surface indentations or pores. In contrast, DHC chains, having hydrophilic groups at both ends, symmetrically adsorb onto the oil-water interface, reducing curvature stress and promoting smoother surfaces. Polymerization and self-assembly proceed concurrently, ultimately forming stable RBC-like microspheres through chain crosslinking and solidification [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe morphology and size of microspheres are synergistically regulated by irradiation dose and monomer concentration. At low irradiation doses (\u0026lt;\u0026thinsp;20 kGy) or low monomer concentrations (\u0026lt;\u0026thinsp;5 wt%), interface stress instability dominated by SHC results in porous structures. Under optimized conditions (20 kGy, 5 wt%), increased DHC proportions facilitate precise formation of RBC-mimetic morphology. Excessive irradiation (\u0026gt;\u0026thinsp;30 kGy), however, leads to over-crosslinking of polymer chains, causing structural homogenization.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn this study, we proposed a facile, efficient, and green synthesis strategy utilizing γ-ray irradiation-assisted radical polymerization coupled with self-assembly reactions to fabricate RBC-like polystyrene particles at room temperature. By systematically optimizing key parameters such as styrene-to-deionized water mass ratio and irradiation dose, precise control over the morphology, size, and uniformity of the RBC-like polystyrene particles was achieved. Our results revealed that the absorbed radiation dose and styrene-to-water mass ratio significantly influence particle morphology and size. Specifically, increasing the irradiation dose generates higher concentrations of oxygen-containing radicals, thus accelerating the self-assembly process and altering particle morphology accordingly.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003eWe appreciate the financial support from the National Natural Science Foundation of China (22276132, U24B20194, 22406135), Gusu Innovation and Entrepreneurship Leading Talent Program Project (ZXL2024403), the Postdoctoral Science Foundation of China (GZC 20231888, 2024M762296) and a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u0026nbsp;\u003c/strong\u003eAll relevant data used to produce these results are included in the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e The authors declare no Conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthorship contribution statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003eThese authors\u0026nbsp;\u003c/strong\u003econtributed equally.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWenhui Fan\u003c/strong\u003e\u003cstrong\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/strong\u003e: design and operation of the experiments and data analysis. \u003cstrong\u003eShuya Zhang\u003c/strong\u003e\u003cstrong\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/strong\u003e: writing and revising the chapters of the article. \u003cstrong\u003eQingyi Ni\u003c/strong\u003e: collecting and organizing the data related to the literature. \u003cstrong\u003eYue Rong\u003c/strong\u003e: organizing the data and drawing the pictures. \u003cstrong\u003eTianping Wang\u003c/strong\u003e\u003csup\u003e*\u003c/sup\u003e: revising the versions of the article ([email protected]). \u003cstrong\u003eHanzhou Liu\u003c/strong\u003e\u003csup\u003e*\u003c/sup\u003e: overall planning and designing the chapters as well as the management of the project ([email protected]) .\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKhalin I, Adarsh N, Schifferer M et al (2022) Size-Selective Transfer of Lipid Nanoparticle-Based Drug Carriers Across the Blood Brain Barrier Via Vascular Occlusions Following Traumatic Brain Injury. 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Chem Soc Rev 40:2402\u0026ndash;2416. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1039/c0cs00216j\u003c/span\u003e\u003cspan address=\"10.1039/c0cs00216j\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\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":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"RBC-like polystyrene particles, irradiation-assisted synthesis, self-assembly, green synthesis","lastPublishedDoi":"10.21203/rs.3.rs-7735322/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7735322/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThis study developed a green γ-ray irradiation-assisted polymerization-self-assembly synergy strategy to fabricate red blood cell (RBC)-like morphology in an additive/template-free aqueous system at room temperature. By tuning the styrene/water mass ratio (2%\u0026ndash;10%) and irradiation dose (5\u0026ndash;100 kGy), we systematically elucidated the regulation mechanisms of microsphere morphology and size. Under optimized conditions (5 wt% styrene, 20 kGy), the microspheres exhibited typical RBC-like structures with an average diameter of 525 nm, hydroxyl-enriched surfaces, and internal hollow cavities. This approach eliminates the reliance on additives and templates in conventional processes.\u003c/p\u003e","manuscriptTitle":"Irradiation-Induced Facile Synthesis and Characterization of Red Blood Cell-Like Polystyrene Particles","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-17 12:05:22","doi":"10.21203/rs.3.rs-7735322/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"db973cb8-1342-41d9-8fe5-744e187a5318","owner":[],"postedDate":"October 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-13T10:38:12+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-17 12:05:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7735322","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7735322","identity":"rs-7735322","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}