{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:59:31Z","timestamp":1785405571251,"version":"3.56.0"},"reference-count":65,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"State Key Laboratory of Polyolefin Catalysis Technology and High Performance Materials","award":["SKLPOC-202502"],"award-info":[{"award-number":["SKLPOC-202502"]}]},{"award":["SKLPOC-202502"],"award-info":[{"award-number":["SKLPOC-202502"]}],"id":[{"id":"https:\/\/ror.org\/04aps9p30","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>Pancreatic ductal adenocarcinoma is highly malignant with poor prognosis. Its dense tumor microenvironment severely limits the efficacy of conventional chemotherapy and causes severe side-effects. Herein, we adopt the established Schiff-base crosslinked thermoresponsive injectable self-healing poly(2-(2-methoxyethoxy)ethyl methacrylate-co-oligo(ethylene glycol) methyl ether methacrylate-co-aldehyde 2-hydroxyethyl methacrylate)\/carboxymethyl chitosan (APMOH\/CMCS) hydrogel as the delivery scaffold. By regulating monomer composition, the volume phase transition temperature (TVPT) of the hydrogel was tuned to around 43 \u00b0C to match the therapeutic temperature requirement. Subsequently, copper\u2013metal organic framework (Cu-MOF) nanoparticles co-loaded with 2,2\u2032-azobis(2-methylimidazoline) dihydrochloride (AIPH) and 2,2\u2032-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) cationic radicals (ABTS\u00b7+) (denoted as AB@Cu-MOF) were uniformly incorporated into the hydrogel network. Under near-infrared (NIR) irradiation, ABTS\u00b7+ acts as a photothermal agent to generate hyperthermia for tumor ablation; the elevated temperature further activates AIPH to produce alkyl radicals, which can oxidize inactivated ABTS back to ABTS\u00b7+ and construct a sustainable photothermal therapy\u2013thermodynamic therapy (PTT-TDT) circulation. Meanwhile, Cu-MOF can consume intracellular glutathione (GSH) to protect active components from deactivation and initiate chemodynamic therapy (CDT) via Fenton-like reactions to produce toxic reactive oxygen species. Benefiting from the thermoresponsive characteristic, the hydrogel undergoes volume shrinkage upon heating, achieving NIR-triggered on-demand drug release with a cumulative release rate of 81.1%. In vitro and in vivo experiments verified that this integrated platform realizes remarkable triple synergistic efficacy of PTT, TDT, and CDT. The tumor volume of the treatment group was merely 13.3% of the control group, and the system also exhibited excellent biocompatibility. Collectively, it offers a feasible and promising intelligent platform for precise local treatment of pancreatic cancer.<\/jats:p>","DOI":"10.3390\/polym18131620","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T15:27:37Z","timestamp":1782746857000},"page":"1620","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Thermoresponsive Injectable Self-Healing Hydrogel Loaded with Self-Regenerating Photothermal Agent for Synergistic Photothermal\u2013Thermodynamic\u2013Chemodynamic Therapy for Pancreatic Cancer"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7928-4339","authenticated-orcid":false,"given":"Junhang","family":"Li","sequence":"first","affiliation":[{"name":"School of Materials Science and Engineering, Tongji University, Shanghai 201804, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5981-9366","authenticated-orcid":false,"given":"Weizhong","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Materials Science and Engineering, Tongji University, Shanghai 201804, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1016\/S0140-6736(25)00261-2","article-title":"Pancreatic cancer","volume":"405","author":"Stoop","year":"2025","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s12029-025-01183-2","article-title":"Trends in the global incidence of pancreatic cancer and a brief review of its histologic and molecular subtypes","volume":"56","author":"Leiphrakpam","year":"2025","journal-title":"J. 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