{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T15:07:33Z","timestamp":1774451253501,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["52276049"],"award-info":[{"award-number":["52276049"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>In situ cancer vaccines activate antitumor immune responses by locally capturing and presenting tumor-derived antigens, in which polymers play a key role as antigen-capturing materials. However, the influence of polymer composition and degree of polymerization (DP) on antigen capture efficiency and protection mechanisms remains insufficiently understood. In this study, the tumor-specific antigen MAGE-A3, highly expressed in esophageal squamous cell carcinoma (ESCC), was employed to investigate antigen capture and stabilization by five representative polymers\u2014chitosan, polyethyleneimine (PEI), alginate, polycaprolactone (PCL), and poly (lactic-co-glycolic acid) (PLGA)\u2014with different DPs, using molecular dynamics simulations and in vitro experiments. All-atom simulations revealed that hydrophobic interactions dominate polymer\u2013antigen binding, while electrostatic interactions from cationic polymers synergistically enhance binding affinity and capture efficiency. Binding free energy analysis showed that van der Waals and electrostatic contributions stabilize the complexes, whereas polar solvation partially counteracts these effects. Experimentally, low-DP chitosan exhibited the highest antigen-capture efficiency (38.9%), attributed to its small molecular size, enabling multipoint binding across the antigen surface. In contrast, high-DP polymers generated pronounced steric hindrance that suppressed antigen\u2013enzyme interactions and inhibited hydrolysis. These findings clarify how polymer composition and chain length jointly regulate antigen capture and protection, providing mechanistic guidance for the rational design of polymer-based in situ cancer vaccines.<\/jats:p>","DOI":"10.3390\/polym18070781","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T13:57:34Z","timestamp":1774447054000},"page":"781","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanisms of Polymer\u2013Antigen Binding and Hydrolysis Inhibition: Molecular Dynamics Simulations and Experimental Measurements"],"prefix":"10.3390","volume":"18","author":[{"given":"Ziyang","family":"Hu","sequence":"first","affiliation":[{"name":"School of Energy and Environmental Engineering, University of Science and Technology Beijing, Beijing 100083, China"},{"name":"Shunde Graduate School, University of Science and Technology Beijing, Foshan 528399, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0457-3415","authenticated-orcid":false,"given":"Kai","family":"Yue","sequence":"additional","affiliation":[{"name":"School of Energy and Environmental Engineering, University of Science and Technology Beijing, Beijing 100083, China"},{"name":"Shunde Graduate School, University of Science and Technology Beijing, Foshan 528399, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weishen","family":"Zhong","sequence":"additional","affiliation":[{"name":"School of Energy and Environmental Engineering, University of Science and Technology Beijing, Beijing 100083, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Genpei","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Energy and Environmental Engineering, University of Science and Technology Beijing, Beijing 100083, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"120726","DOI":"10.1016\/j.biomaterials.2021.120726","article-title":"P22 virus-like particles as an effective antigen delivery nanoplatform for cancer immunotherapy","volume":"271","author":"Li","year":"2021","journal-title":"Biomaterials"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"112120","DOI":"10.1016\/j.isci.2025.112120","article-title":"Combination therapy with alisertib enhances the antitumor immunity induced by a liver cancer vaccine","volume":"28","author":"Xue","year":"2025","journal-title":"iScience"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ding, K., Mou, P., Wang, Z., Liu, S., Liu, J., Lu, H., and Yu, G. 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