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Herein, cisplatin and 17AAG were loaded into a thermoresponsive biodegradable polyurethane (PU) hydrogel, forming the CDDP\/17AAG@PU system. This system showed favorable in vitro sustained release properties, controllable thermosensitive gelation at 43\u00b0C and excellent biocompatibility. Benefiting from the hydrogel's sustained release at safe doses, compared with the free drug group, this system significantly reduced serum biochemical abnormalities, as indicated by lower serum ALT\/CREA levels and less apoptosis of normal intestinal cells. Moreover, its thermosensitive treatment enhanced antitumor efficacy by promoting DNA cross\u2010linking and inhibiting oncogenic signaling\u2010related proteins (p\u2010PI3K, p\u2010AKT, MMP2). In vivo experiments showed it more effectively inhibited CRC\u2010PM compared to single\u2010drug treatment and the control group. In conclusion, the safe, degradable CDDP\/17AAG@PU system spreads to cover CRC\u2010PM tumors at 37\u00b0C and gels rapidly at 43\u00b0C (clinical HIPEC temperature). It reduces antitumor drug induced hepatorenal toxicity, exerts good efficacy against CRC\u2010PM and thus hold considerable potential for clinical translation.<\/jats:p>","DOI":"10.1002\/adhm.202504662","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T05:13:52Z","timestamp":1775452432000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synergistic Thermochemotherapy via Injectable Polyurethane Hydrogel Co\u2010Delivering Cisplatin and 17AAG for Peritoneal Metastasis of Colorectal Cancer"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6647-4100","authenticated-orcid":false,"given":"Xiangdong","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery School of Medicine Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital University of Electronic Science and Technology of China  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