{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:02:48Z","timestamp":1790254968935,"version":"4.1.0"},"reference-count":37,"publisher":"American Chemical Society (ACS)","issue":"38","license":[{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2024-553"],"award-info":[{"award-number":["075-15-2024-553"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Anticancer polymers represent a novel, promising class of therapeutical agents aimed to combat emerging multidrug resistance. Here, we employ atomic-scale computer simulations to explore for the first time the molecular-level impact of anticancer polymers on model cancerous membranes. To this end, we focused on methacrylate-based random copolymers with proven anticancer activity. Our computational findings show that phosphatidylserine lipids on the surface of cancerous membranes serve as the primary targets for protonated amine groups of anticancer polymers. Adsorption of cationic anticancer polymers induces the lateral ordering and clustering of anionic phosphatidylserines in line with existing experimental data. Embedding polymers into the membrane results in an expansion of the membrane, which is accompanied by a drop in its thickness and by disordering of lipid acyl chains. Within the membrane, anticancer polymers adopt a comb-like conformation with the backbones being buried in the hydrophobic membrane core and the protonated side groups being bound to lipid phosphate groups. The polymer-induced thinning of the membrane turns out to depend non-monotonically on polymer hydrophobicity. This highlights the importance of a balance between the overall charge and the hydrophobicity of polymers for promoting anticancer activity. Although spontaneous pore formation was shown to be beyond the time scales accessible through atomic-scale simulations, membrane thinning can be considered a first step toward the nucleation of transmembrane pores and subsequent membrane collapse. Our electroporation tests showed that the membrane became more prone to poration upon adsorption of anticancer polymers. All in all, our computational findings provide valuable microscopic information for further optimization of anticancer polymeric agents.<\/jats:p>","DOI":"10.1021\/acs.jpcb.6c03563","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T16:02:23Z","timestamp":1789228943000},"page":"9816-9825","source":"Crossref","is-referenced-by-count":0,"title":["Impact of Anticancer\nPolymers on Model Cancerous Membranes:\nMolecular-Level Insight from Computer Simulations"],"prefix":"10.1021","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9834-1617","authenticated-orcid":true,"given":"Andrey A.","family":"Gurtovenko","sequence":"first","affiliation":[{"name":"Branch of Petersburg Nuclear Physics Institute Named By B. P. Konstantinov of National Research Centre \u201cKurchatov Institute\u201d \u2212 Institute of Macromolecular Compounds , Bolshoi Prospect V.O. 31 , ,","place":["Saint Petersburg, Russia, 199004"]},{"name":"St. Petersburg State University , , 7\/9 Universitetskaya Naberezhnaya , ,","place":["Saint Petersburg, Russia, 199034"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2448-8584","authenticated-orcid":true,"given":"Victor M.","family":"Nazarychev","sequence":"additional","affiliation":[{"name":"Branch of Petersburg Nuclear Physics Institute Named By B. P. Konstantinov of National Research Centre \u201cKurchatov Institute\u201d \u2212 Institute of Macromolecular Compounds , Bolshoi Prospect V.O. 31 , ,","place":["Saint Petersburg, Russia, 199004"]},{"name":"St. Petersburg State University , , 7\/9 Universitetskaya Naberezhnaya , ,","place":["Saint Petersburg, Russia, 199034"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,12]]},"reference":[{"key":"2026092408094749800_cit1","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1038\/s41571-025-01059-1","article-title":"Understanding\nand overcoming multidrug resistance in cancer","volume":"22","author":"Ge","year":"2025","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"2026092408094749800_cit2","doi-asserted-by":"publisher","first-page":"120078","DOI":"10.1016\/j.biomaterials.2020.120078","article-title":"Synthetic macromolecules as therapeutics\nthat overcome resistance in cancer and microbial infection","volume":"252","author":"Tan","year":"2020","journal-title":"Biomaterials"},{"key":"2026092408094749800_cit3","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.bioactmat.2023.08.007","article-title":"From oncolytic peptides\nto oncolytic polymers: A new paradigm for\noncotherapy","volume":"31","author":"Liu","year":"2024","journal-title":"Bioact. Mater."},{"key":"2026092408094749800_cit4","doi-asserted-by":"publisher","DOI":"10.1002\/wnan.1866","article-title":"Biomimetic\nantimicrobial polymers\n\u2013 Design, characterization, antimicrobial, and novel applications","volume":"15","author":"Takahashi","year":"2023","journal-title":"WIREs Nanomedicine and Nanobiotechnology"},{"key":"2026092408094749800_cit5","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1007\/s41048-018-0080-0","article-title":"Detection\nof cancer cells based on glycolytic-regulated surface electrical charges","volume":"5","author":"Le","year":"2019","journal-title":"Biophys. Reports"},{"key":"2026092408094749800_cit6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fcell.2020.571237","article-title":"New insights\ninto targeting membrane lipids for cancer therapy","volume":"8","author":"Preta","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"2026092408094749800_cit7","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1038\/s41598-018-36608-5","article-title":"Anticancer polymers\ndesigned for killing dormant prostate cancer cells","volume":"9","author":"Takahashi","year":"2019","journal-title":"Sci. Rep."},{"key":"2026092408094749800_cit8","doi-asserted-by":"publisher","first-page":"1632","DOI":"10.1021\/bm300342u","article-title":"Cationic spacer arm design strategy\nfor control of antimicrobial activity and conformation of amphiphilic\nmethacrylate random copolymers","volume":"13","author":"Palermo","year":"2012","journal-title":"Biomacromolecules"},{"key":"2026092408094749800_cit9","doi-asserted-by":"publisher","first-page":"084902","DOI":"10.1063\/1.4893440","article-title":"Interaction of multiple biomimetic\nantimicrobial polymers with model bacterial membranes","volume":"141","author":"Baul","year":"2014","journal-title":"J. Chem. Phys."},{"key":"2026092408094749800_cit10","doi-asserted-by":"publisher","first-page":"7665","DOI":"10.1039\/C7SM01211J","article-title":"Influence\nof lipid composition of model membranes on\nmethacrylate antimicrobial polymer\u2013membrane interactions","volume":"13","author":"Baul","year":"2017","journal-title":"Soft Matter"},{"key":"2026092408094749800_cit11","doi-asserted-by":"publisher","first-page":"2090","DOI":"10.1039\/D0SM01896A","article-title":"Towards designing\nglobular antimicrobial\npeptide mimics: role of polar functional groups in biomimetic ternary\nantimicrobial polymers","volume":"17","author":"Rani","year":"2021","journal-title":"Soft Matter"},{"key":"2026092408094749800_cit12","doi-asserted-by":"publisher","first-page":"4406","DOI":"10.1021\/acs.langmuir.3c00031","article-title":"Role of lipid packing defects in\ndetermining membrane interactions of antimicrobial polymers","volume":"39","author":"Sikdar","year":"2023","journal-title":"Langmuir"},{"key":"2026092408094749800_cit13","doi-asserted-by":"publisher","first-page":"7134","DOI":"10.1021\/acs.jpcb.5c00321","article-title":"The role of\nnegatively charged groups\nin antimicrobial cationic peptide mimics: insights into membrane interactions","volume":"129","author":"Saiba","year":"2025","journal-title":"J. Phys. Chem. B"},{"key":"2026092408094749800_cit14","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1186\/s12964-025-02090-6","article-title":"Dys-regulated\nphosphatidylserine externalization as a cell intrinsic immune escape\nmechanism in cancer","volume":"23","author":"Pulica","year":"2025","journal-title":"Cell Commun. Signal."},{"key":"2026092408094749800_cit15","doi-asserted-by":"publisher","first-page":"3144","DOI":"10.1021\/ci300363c","article-title":"Automation of\nthe CHARMM General\nForce Field (CGenFF) I: Bond perception and atom typing","volume":"52","author":"Vanommeslaeghe","year":"2012","journal-title":"J. Chem. Inf. Model."},{"key":"2026092408094749800_cit16","doi-asserted-by":"publisher","first-page":"7830","DOI":"10.1021\/jp101759q","article-title":"Update of the CHARMM\nall-atom additive force field\nfor lipids: validation on six lipid types","volume":"114","author":"Klauda","year":"2010","journal-title":"J.\nPhys. Chem. 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Theory Comput."},{"key":"2026092408094749800_cit33","doi-asserted-by":"publisher","first-page":"12462","DOI":"10.1021\/ja0624321","article-title":"Lipids out of equilibrium: energetics\nof desorption\nand pore mediated flip-flop","volume":"128","author":"Tieleman","year":"2006","journal-title":"J. Am. Chem. Soc."},{"key":"2026092408094749800_cit34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0144611","article-title":"Comparative evaluation of the antimicrobial activity\nof different antimicrobial peptides against a range of pathogenic\nbacteria","volume":"10","author":"Ebbensgaard","year":"2015","journal-title":"PLoS One"},{"key":"2026092408094749800_cit35","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.3892\/etm.2013.1056","article-title":"Expression\nand characterization of cecropinXJ, a bioactive antimicrobial peptide\nfrom Bombyx mori (Bombycidae, Lepidoptera) in Escherichia coli","volume":"5","author":"Xia","year":"2013","journal-title":"Exp. Ther. Med."},{"key":"2026092408094749800_cit36","doi-asserted-by":"publisher","first-page":"3346","DOI":"10.1016\/S0006-3495(01)75968-1","article-title":"Polylysine-induced 2H NMR-observable domains\nin phosphatidylserine\/phosphatidylcholine lipid bilayers","volume":"81","author":"Franzin","year":"2001","journal-title":"Biophys. J."},{"key":"2026092408094749800_cit37","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1007\/s00249-006-0080-8","article-title":"Interaction of poly(L-lysines)\nwith negatively charged membranes:\nAn FT-IR and DSC study","volume":"36","author":"Schwieger","year":"2007","journal-title":"Eur. Biophys. J."}],"container-title":["The Journal of Physical\nChemistry B"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jpcb.6c03563","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jpcbfk\/article-pdf\/130\/38\/9816\/68492260\/acs.jpcb.6c03563.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jpcbfk\/article-pdf\/130\/38\/9816\/68492260\/acs.jpcb.6c03563.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:25:39Z","timestamp":1790252739000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jpcbfk\/article\/130\/38\/9816\/5428920\/Impact-of-Anticancer-Polymers-on-Model-Cancerous"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,12]]},"references-count":37,"journal-issue":{"issue":"38","published-online":{"date-parts":[[2026,9,12]]},"published-print":{"date-parts":[[2026,9,24]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jpcb.6c03563","relation":{},"ISSN":["1520-6106","1520-5207"],"issn-type":[{"value":"1520-6106","type":"print"},{"value":"1520-5207","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,12]]}}}