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However, current therapeutic strategies rarely address infection-associated complications, highlighting the need for multifunctional biomaterials capable of simultaneously targeting tumor cells and pathogenic bacteria. Herein, retinoic acid (RA)-functionalized chitosan polycationic conjugates were well engineered to achieve integrated anticancer and antimicrobial activity. The incorporation of quaternary ammonium groups together with hydrophobic RA moieties enabled the rational regulation of charge density and hydrophilic\u2013hydrophobic balance, resulting in improved aqueous solubility, bioactivity, and biocompatibility. The optimized conjugate inhibited melanoma cell proliferation (IC50 = 4 \u03bcg\/mL) and exhibited broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria, with MIC values of 4\u201332 \u03bcg\/mL. Mechanistic studies suggested that the polycationic conjugates act through multiple coordinated mechanisms, including membrane disruption, RAR\/RXR-related signaling, ROS generation, and necrosis\/apoptosis induction. In vivo experiments further demonstrated significant antitumor suppression (\u223c70% reduction in tumor volume) together with effective inhibition of S. aureus infection at wound sites (\u223c1.5-log reduction). These findings highlight RA-functionalized chitosan polycations as a promising multifunctional biomaterial system for melanoma therapy while addressing infection-associated complications.<\/jats:p>","DOI":"10.1021\/acsbiomaterials.6c00535","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T21:41:24Z","timestamp":1782855684000},"page":"3353-3365","source":"Crossref","is-referenced-by-count":0,"title":["Retinoic Acid-Functionalized Chitosan Polycationic Conjugates for Integrated Melanoma Therapy and Antibacterial Infection Control"],"prefix":"10.1021","volume":"12","author":[{"given":"Sijin","family":"Chen","sequence":"first","affiliation":[{"name":"Tongji University , , 4800 Caoan Road , ,","place":["Shanghai, China, 201804"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"He","sequence":"additional","affiliation":[{"name":"Shanghai Skin Disease Hospital, School of Medicine, Tongji University , , ,","place":["Shanghai, China, 200331"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyun","family":"Shen","sequence":"additional","affiliation":[{"name":"Shanghai Skin Disease Hospital, School of Medicine, Tongji University , , ,","place":["Shanghai, China, 200331"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusheng","family":"Qian","sequence":"additional","affiliation":[{"name":"Tongji University , , 4800 Caoan Road , ,","place":["Shanghai, China, 201804"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuting","family":"Huang","sequence":"additional","affiliation":[{"name":"Tongji University , , 4800 Caoan Road , ,","place":["Shanghai, China, 201804"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Tongji University , , ,","place":["Shanghai, China, 200331"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8176-4429","authenticated-orcid":true,"given":"Chuncai","family":"Zhou","sequence":"additional","affiliation":[{"name":"Tongji University , , 4800 Caoan Road , ,","place":["Shanghai, China, 201804"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5749-6153","authenticated-orcid":true,"given":"Decheng","family":"Wan","sequence":"additional","affiliation":[{"name":"Tongji University , , 4800 Caoan Road , ,","place":["Shanghai, China, 201804"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"2026101319081091100_cit1","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2025.1610661","article-title":"Global burden of skin cancer and its subtypes: a comprehensive analysis from 1990 to 2021 with projections to 2040","volume":"13","author":"Chen","year":"2025","journal-title":"Front. 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