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We demonstrate that transfection enhancement is driven by concentration-dependent synergism between membrane accumulation and endosomal escape. Guided by this mechanism, a half-volume transfection strategy was established to transiently elevate plasmid concentration without compromising cell viability, enabling superior lentivirus yield and purity. These findings define plasmid concentration as a previously overlooked regulatory axis in nanoparticle-mediated gene delivery and position HPAE as a high-performance platform for scalable therapeutic vector production.<\/jats:p>","DOI":"10.3390\/polym18091015","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T12:54:08Z","timestamp":1776862448000},"page":"1015","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Concentration of DNA at the Cell Surface Dictates Transfection Efficacy: A Hyperbranched Poly(\u03b2-Amino Ester) Mediated Strategy for Enhanced Lentivirus Production"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9711-287X","authenticated-orcid":false,"given":"Miao","family":"Wei","sequence":"first","affiliation":[{"name":"School of Medicine, Anhui University of Science and Technology, Huainan 232001, China"},{"name":"Institute of Precision Medicine (AUST-IPM), Anhui University of Science and Technology, Huainan 232001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6000-8974","authenticated-orcid":false,"given":"Liang","family":"Yao","sequence":"additional","affiliation":[{"name":"Charles Institute of Dermatology, University College Dublin, D04 V1W8 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyue","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, Anhui University of Science and Technology, Huainan 232001, China"},{"name":"Institute of Precision Medicine (AUST-IPM), Anhui University of Science and Technology, Huainan 232001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meilin","family":"Guo","sequence":"additional","affiliation":[{"name":"ST PHI Therapeutics Co., Ltd., Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haonan","family":"Li","sequence":"additional","affiliation":[{"name":"ACROBiosystems Inc., Beijing 100176, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang","family":"Chen","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of New Drug Development for Central Nervous System Diseases, School of Medicine, Taizhou University, Taizhou 318000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8702-3859","authenticated-orcid":false,"given":"Xianqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Charles Institute of Dermatology, University College Dublin, D04 V1W8 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine (AUST-IPM), Anhui University of Science and Technology, Huainan 232001, China"},{"name":"Charles Institute of Dermatology, University College Dublin, D04 V1W8 Dublin, Ireland"},{"name":"School of Public Health, Anhui University of Science and Technology, Huainan 232001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5053-0611","authenticated-orcid":false,"given":"Wenxin","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine (AUST-IPM), Anhui University of Science and Technology, Huainan 232001, China"},{"name":"Charles Institute of Dermatology, University College Dublin, D04 V1W8 Dublin, Ireland"},{"name":"School of Public Health, Anhui University of Science and Technology, Huainan 232001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonglei","family":"He","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine (AUST-IPM), Anhui University of Science and Technology, Huainan 232001, China"},{"name":"Zhejiang Key Laboratory of New Drug Development for Central Nervous System Diseases, School of Medicine, Taizhou University, Taizhou 318000, China"},{"name":"School of Public Health, Anhui University of Science and Technology, Huainan 232001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/s41575-022-00729-0","article-title":"Gene Therapy for Liver Diseases\u2014Progress and Challenges","volume":"20","author":"Zabaleta","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Godbout, K., and Tremblay, J.P. (2023). Prime Editing for Human Gene Therapy: Where Are We Now?. Cells, 12.","DOI":"10.3390\/cells12040536"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e202422134","DOI":"10.1002\/anie.202422134","article-title":"Precise PBAEs: A Highly Efficient Single-Molecularly Defined Gene-Delivery System","volume":"64","author":"Ma","year":"2025","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6409","DOI":"10.7150\/thno.77089","article-title":"Strategies for Accelerating Osteogenesis through Nanoparticle-Based DNA\/Mitochondrial Damage Repair","volume":"12","author":"Kim","year":"2022","journal-title":"Theranostics"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e1741","DOI":"10.1002\/wnan.1741","article-title":"Nanoparticle Mediated RNA Delivery for Wound Healing","volume":"14","author":"Kolanthai","year":"2022","journal-title":"Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4597","DOI":"10.1039\/D5BM00711A","article-title":"Nanotechnological Approaches for the Targeted Delivery of CRISPR-Cas Systems for Genomic Modifications, Biomolecular Sensing, and Precision Medicine","volume":"13","author":"Baig","year":"2025","journal-title":"Biomater. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1186\/s12951-023-02044-5","article-title":"Emerging Non-Viral Vectors for Gene Delivery","volume":"21","author":"Wang","year":"2023","journal-title":"J. Nanobiotechnol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e2001238","DOI":"10.1002\/adhm.202001238","article-title":"Is Viral Vector Gene Delivery More Effective Using Biomaterials?","volume":"10","author":"Wang","year":"2021","journal-title":"Adv. Healthc. Mater."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6862","DOI":"10.1039\/D2BM01001A","article-title":"Recent Advances in Nanotechnology Approaches for Non-Viral Gene Therapy","volume":"10","author":"Jiang","year":"2022","journal-title":"Biomater. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1021\/acsami.3c14714","article-title":"Development of Polymer-Lipid Hybrid Nanoparticles for Large-Sized Plasmid DNA Transfection","volume":"16","author":"Maeki","year":"2024","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Chopra, S., Ruzgys, P., Maciulevi\u010dius, M., Jakutavi\u010di\u016bt\u0117, M., and \u0160atkauskas, S. (2020). Investigation of Plasmid DNA Delivery and Cell Viability Dynamics for Optimal Cell Electrotransfection In Vitro. Appl. Sci., 10.","DOI":"10.3390\/app10176070"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.actbio.2021.01.042","article-title":"The Varied Influences of Cell Adhesion and Spreading on Gene Transfection of Mesenchymal Stem Cells on a Micropatterned Substrate","volume":"125","author":"Wang","year":"2021","journal-title":"Acta Biomater."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1038\/78523","article-title":"Enhancement of Transfection by Physical Concentration of DNA at the Cell Surface","volume":"18","author":"Luo","year":"2000","journal-title":"Nat. Biotechnol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1021\/acsmacrolett.3c00152","article-title":"Branch Unit Distribution Matters for Gene Delivery","volume":"12","author":"Li","year":"2023","journal-title":"ACS Macro Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e1600102","DOI":"10.1126\/sciadv.1600102","article-title":"The Transition from Linear to Highly Branched Poly(\u03b2-Amino Ester)s: Branching Matters for Gene Delivery","volume":"2","author":"Zhou","year":"2016","journal-title":"Sci. Adv."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.jconrel.2024.01.026","article-title":"Enhanced Gene Transfection and Induction of Apoptosis in Melanoma Cells by Branched Poly(\u03b2-Amino Ester)s with Uniformly Distributed Branching Units","volume":"367","author":"Chu","year":"2024","journal-title":"J. Control. Release"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.jconrel.2024.04.030","article-title":"Superior COL7A1 and TGM1 Gene Expression in Difficult-to-Transfect Skin Cell Mediated by Highly Branched Poly(\u03b2-Amino Esters) through Stepwise Fractionation","volume":"370","author":"Pan","year":"2024","journal-title":"J. Control. Release"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"113668","DOI":"10.1016\/j.jconrel.2025.113668","article-title":"Ultra-High Gene Transfection Efficiency in Suspension Cells Mediated by Highly Branched-Linear Poly(\u03b2-Amino Ester)s","volume":"382","author":"Wang","year":"2025","journal-title":"J. Control. Release"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.jconrel.2024.01.046","article-title":"Backbone Cationized Highly Branched Poly(\u03b2-Amino Ester)s as Enhanced Delivery Vectors in Non-Viral Gene Therapy","volume":"367","author":"Li","year":"2024","journal-title":"J. Control. Release"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"102314","DOI":"10.1016\/j.omtn.2024.102314","article-title":"Simple Improvements in Vector Design Afford Substantial Gains in AAV Delivery of Aggregation-Slowing A\u03b2 Variants","volume":"35","author":"Borgenheimer","year":"2024","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"131495","DOI":"10.1016\/j.biortech.2024.131495","article-title":"Optimization of Fungal Secondary Metabolites Production via Response Surface Methodology Coupled with Multi-Parameter Optimized Artificial Neural Network Model","volume":"413","author":"Shu","year":"2024","journal-title":"Bioresour. Technol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.copbio.2021.12.009","article-title":"Leveraging rAAV Bioprocess Understanding and next Generation Bioanalytics Development","volume":"74","author":"Escandell","year":"2022","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e202422278","DOI":"10.1002\/anie.202422278","article-title":"Ultrasound-Activated Theranostic Materials and Their Bioapplications","volume":"64","author":"Zhu","year":"2025","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Liu, J., Fu, S., Xie, J., Zhang, J., Pan, J., Chu, C., Liu, G., and Ju, S. (2022). Application of Self-Assembly Nanoparticles Based on DVDMS for Fenton-Like Ion Delivery and Enhanced Sonodynamic Therapy. Biosensors, 12.","DOI":"10.3390\/bios12040255"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9368","DOI":"10.1021\/acs.nanolett.4c02440","article-title":"Tailoring Highly Branched Poly(\u03b2-Amino Ester)s for Efficient and Organ-Selective mRNA Delivery","volume":"24","author":"Yong","year":"2024","journal-title":"Nano Lett."},{"key":"ref_26","first-page":"1136","article-title":"Gal8 Visualization of Endosome Disruption Predicts Carrier-Mediated Biologic Drug Intracellular Bioavailability","volume":"13","author":"Kilchrist","year":"2019","journal-title":"ACS Nano"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"113842","DOI":"10.1016\/j.addr.2021.113842","article-title":"Highly Branched Poly(\u03b2-Amino Ester)s for Gene Delivery in Hereditary Skin Diseases","volume":"176","author":"Zeng","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Wang, X., Alshehri, F., Manzanares, D., Li, Y., He, Z., Qiu, B., Zeng, M., A, S., Lara-S\u00e1ez, I., and Wang, W. (2021). Development of Minicircle Vectors Encoding COL7A1 Gene with Human Promoters for Non-Viral Gene Therapy for Recessive Dystrophic Epidermolysis Bullosa. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222312774"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Li, Y., He, Z., Lyu, J., Wang, X., Qiu, B., Lara-S\u00e1ez, I., Zhang, J., Zeng, M., Xu, Q., and A, S. (2022). Hyperbranched Poly(\u03b2-Amino Ester)s (HPAEs) Structure Optimisation for Enhanced Gene Delivery: Non-Ideal Termination Elimination. Nanomaterials, 12.","DOI":"10.3390\/nano12213892"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jconrel.2024.02.002","article-title":"Enhancing Gene Transfection of Poly(\u03b2-Amino Ester)s through Modulation of Amphiphilicity and Chain Sequence","volume":"368","author":"Li","year":"2024","journal-title":"J. Control. Release"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e202319003","DOI":"10.1002\/anie.202319003","article-title":"Self-Reporting and Biodegradable Thermosetting Solid Polymer Electrolyte","volume":"63","author":"Zhou","year":"2024","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.2147\/IJN.S287434","article-title":"Optimization, Characterization and in Vivo Evaluation of Paclitaxel-Loaded Folate-Conjugated Superparamagnetic Iron Oxide Nanoparticles","volume":"16","author":"Gui","year":"2021","journal-title":"Int. J. Nanomed."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e2411293","DOI":"10.1002\/smll.202411293","article-title":"pH-Dependent Structural Changes in Polyethyleneimine Affect Its Gene Transfection Efficiency","volume":"21","author":"Sharma","year":"2025","journal-title":"Small"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"112561","DOI":"10.1016\/j.colsurfb.2022.112561","article-title":"Gelatin Nanofiber Mats with Lipofectamine\/Plasmid DNA Complexes for in Vitro Genome Editing","volume":"216","author":"Furuno","year":"2022","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5697","DOI":"10.1021\/acs.nanolett.1c01421","article-title":"Size-Controlled and Shelf-Stable DNA Particles for Production of Lentiviral Vectors","volume":"21","author":"Hu","year":"2021","journal-title":"Nano Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1021\/cbmi.4c00088","article-title":"Tumor Spheroid Uptake of Fluorescent Nanodiamonds Is Limited by Mass Density: A 4D Light-Sheet Assay","volume":"3","author":"Niora","year":"2025","journal-title":"Chem. Biomed. Imaging"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"139194","DOI":"10.1016\/j.chemosphere.2023.139194","article-title":"Effects of Size and Surface Charge on the Sedimentation of Nanoplastics in Freshwater","volume":"336","author":"Zhu","year":"2023","journal-title":"Chemosphere"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1039\/D1BM01684A","article-title":"Self-Immolative Polyplexes for DNA Delivery","volume":"10","author":"Sirianni","year":"2022","journal-title":"Biomater. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1021\/acsmacrolett.2c00638","article-title":"Diblock Copolymer Stabilized Liquid Metal Nanoparticles: Particle Settling Behavior and Application to 3D Printing","volume":"12","author":"Corrigan","year":"2023","journal-title":"ACS Macro Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"17559","DOI":"10.1039\/D5NR00699F","article-title":"Suspension Stability of Aluminum-Based Adjuvants","volume":"17","author":"Liang","year":"2025","journal-title":"Nanoscale"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"212984","DOI":"10.1016\/j.bioadv.2022.212984","article-title":"pH-Sensitive, Tail-Modified, Ester-Linked Ionizable Cationic Lipids for Gene Delivery","volume":"139","author":"Zou","year":"2022","journal-title":"Biomater. Adv."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"44376","DOI":"10.1021\/acsami.4c10144","article-title":"A Photothermal Polymeric Platform for Efficient and Safe Gene Transfection: When Polyethylenimine Collaborates with Indocyanine Green","volume":"16","author":"Lu","year":"2024","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"117640","DOI":"10.1016\/j.biopha.2024.117640","article-title":"Systematic Insights into Cell Density-Dependent Transcriptional Responses upon Medium Replacements","volume":"181","author":"Romero","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9369","DOI":"10.1093\/nar\/gkae640","article-title":"High Ionic Strength Vector Formulations Enhance Gene Transfer to Airway Epithelia","volume":"52","author":"Cooney","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2586","DOI":"10.1021\/acs.biomac.2c00282","article-title":"Strategic Insights into Engineering Parameters Affecting Cell Type-Specific Uptake of DNA-Based Nanomaterials","volume":"23","author":"Koga","year":"2022","journal-title":"Biomacromolecules"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s12951-021-00801-y","article-title":"Improved Gene Delivery to K-562 Leukemia Cells by Lipoic Acid Modified Block Copolymer Micelles","volume":"19","author":"Richter","year":"2021","journal-title":"J. Nanobiotechnol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"102989","DOI":"10.1016\/j.cis.2023.102989","article-title":"Cold Atmospheric Plasma Mediated Cell Membrane Permeation and Gene Delivery-Empirical Interventions and Pertinence","volume":"320","author":"Sreedevi","year":"2023","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"101160","DOI":"10.1016\/j.plipres.2022.101160","article-title":"Need for More Focus on Lipid Species in Studies of Biological and Model Membranes","volume":"86","author":"Skotland","year":"2022","journal-title":"Prog. Lipid Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.jconrel.2024.02.024","article-title":"Efficient Gene Delivery by Multifunctional Star Poly (\u03b2-Amino Ester)s into Difficult-to-Transfect Macrophages for M1 Polarization","volume":"368","author":"Bo","year":"2024","journal-title":"J. Control. Release"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"36667","DOI":"10.1021\/acsami.3c05010","article-title":"Artificial Intelligence (AI)-Aided Structure Optimization for Enhanced Gene Delivery: The Effect of the Polymer Component Distribution (PCD)","volume":"15","author":"Li","year":"2023","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Jiang, S., Zu, C., Wang, B., and Zhong, Y. (2025). Enhancing DNA Vaccine Delivery Through Stearyl-Modified Cell-Penetrating Peptides: Improved Antigen Expression and Immune Response In Vitro and In Vivo. Vaccines, 13.","DOI":"10.3390\/vaccines13010094"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"116893","DOI":"10.1016\/j.biopha.2024.116893","article-title":"Internalization of PEI-Based Complexes in Transient Transfection of HEK293 Cells Is Triggered by Coalescence of Membrane Heparan Sulfate Proteoglycans like Glypican-4","volume":"176","author":"Romero","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"104070","DOI":"10.1016\/j.drudis.2024.104070","article-title":"Endolysosomal Trapping of Therapeutics and Endosomal Escape Strategies","volume":"29","author":"Ahmad","year":"2024","journal-title":"Drug Discov. Today"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.ymben.2025.03.011","article-title":"Multi-Omics Driven Genome-Scale Metabolic Modeling Improves Viral Vector Yield in HEK293","volume":"91","author":"Zehetner","year":"2025","journal-title":"Metab. Eng."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Shen, W., Liu, S., and Ou, L. (2022). rAAV Immunogenicity, Toxicity, and Durability in 255 Clinical Trials: A Meta-Analysis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1001263"}],"container-title":["Polymers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4360\/18\/9\/1015\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T08:21:35Z","timestamp":1778142095000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4360\/18\/9\/1015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,22]]},"references-count":55,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["polym18091015"],"URL":"https:\/\/doi.org\/10.3390\/polym18091015","relation":{},"ISSN":["2073-4360"],"issn-type":[{"value":"2073-4360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,22]]}}}