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Dense extracellular matrix (ECM) impedes nanoparticle penetration, while lactate accumulation induces immunosuppression and reinforces stromal remodeling, leading to suboptimal treatment outcomes. Herein, we report an enzyme-integrated semiconducting polymer nanoplatform (PCLN) for synchronous remodeling of physical and metabolic tumor barriers to potentiate second near-infrared (NIR-II) photoimmunotherapy. The nanoplatform is constructed by crosslinking a pH-responsive semiconducting polymer nanoparticle (poly(aniline-co-aniline-N-propylsulfonic acid) (PSPA) with collagenase and lactate oxidase via a reactive oxygen species (ROS)-cleavable linker, enabling spatiotemporally controlled activation. Upon tumor accumulation, ROS-triggered disassembly restores enzymatic activity, leading to simultaneous ECM degradation and lactate depletion, thereby alleviating stromal and metabolic barriers. The released ultrasmall PSPA further enhances tumor penetration, while its NIR-II photothermal effect induces immunogenic cell death. This synergistic strategy effectively reprograms the TME by suppressing lactate metabolism, amplifying oxidative stress, and relieving stromal constraints. Consequently, PCLN combined with NIR-II laser irradiation achieves near-complete tumor inhibition, remodels the immunosuppressive TME, and potentiates antitumor immune responses. This work provides a versatile strategy for overcoming multiple TME barriers and establishes a programmable nanoplatform for potentiated NIR-II photoimmunotherapy.<\/jats:p>","DOI":"10.1021\/acsami.6c13476","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T23:37:28Z","timestamp":1788219448000},"page":"47526-47541","source":"Crossref","is-referenced-by-count":0,"title":["Enzyme-Integrated Semiconducting Polymer Nanoplatform Remodels Physical and Metabolic Tumor Barriers for Potentiated Second Near-Infrared Region Photoimmunotherapy"],"prefix":"10.1021","volume":"18","author":[{"given":"Peijia","family":"Ma","sequence":"first","affiliation":[{"name":"Shenzhen University , , ,","place":["Shenzhen, China, 518055"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Shenzhen University , , ,","place":["Shenzhen, China, 518055"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankang","family":"Mu","sequence":"additional","affiliation":[{"name":"Shenzhen University , , ,","place":["Shenzhen, China, 518055"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoguo","family":"Ye","sequence":"additional","affiliation":[{"name":"Shenzhen University , , ,","place":["Shenzhen, China, 518055"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongchao","family":"Han","sequence":"additional","affiliation":[{"name":"Shenzhen University , , ,","place":["Shenzhen, China, 518055"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien Ting","family":"Chin","sequence":"additional","affiliation":[{"name":"Shenzhen University , , ,","place":["Shenzhen, China, 518055"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7635-0950","authenticated-orcid":true,"given":"Jiayingzi","family":"Wu","sequence":"additional","affiliation":[{"name":"Shenzhen University , , ,","place":["Shenzhen, China, 518055"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"issue":"1","key":"2026091612074207300_cit1","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/nrc.2016.108","article-title":"Cancer Nanomedicine: Progress, Challenges and Opportunities","volume":"17","author":"Shi","year":"2017","journal-title":"Nat. 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