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Herein, we develop a photothermal strategy for in vivo protein corona reprogramming to enhance nanoparticle (NP) accumulation and anticancer efficacy. This strategy utilizes theranostic BBT (4,7\u2010bis(4\u2010(2\u2010ethylhexyl)thiophen\u20102\u2010yl)benzobis[c][1,2,5]thiadiazole) NPs featuring superior photothermal conversion, stacking\u2010induced charge transfer\u2010enhanced Raman scattering (SICTERS), and photoacoustic imaging capabilities, enabling localized photothermal heating for controlled protein corona regulation and real\u2010time efficacy monitoring. In orthotopic breast cancer models, we demonstrated that localized photothermal heating dynamically reprogrammed protein corona composition in an irradiation time\u2010dependent manner, resulting in significant enrichment of dysopsonins (e.g., albumin and apolipoprotein A\u2010I) on BBT NPs. This compositional remodeling effectively shielded BBT NPs from the mononuclear phagocyte system surveillance. Real\u2010time Raman and photoacoustic imaging revealed that photothermally regulated BBT NPs exhibited a significantly prolonged circulation half\u2010life (from 19.3 to 48.4\u00a0h), reduced hepatic sequestration, and enhanced tumor accumulation relative to untreated controls. Consequently, this in vivo protein corona reprogramming strategy notably improved the photothermal antitumor efficacy of BBT NPs. This work establishes photothermal regulation as a promising modality for optimizing NP delivery efficiency, with broad implications for enhancing nanomedicine\u2010based cancer therapy.<\/jats:p>","DOI":"10.1002\/smtd.70960","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T04:31:56Z","timestamp":1787200316000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Photothermal Reprogramming of In Vivo Protein Corona on Nanoparticles for Enhanced Breast Cancer Nanotherapy"],"prefix":"10.1002","volume":"10","author":[{"given":"Haoze","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Chemical Biology, and Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, School of Medicine Shanghai Jiao Tong University  Shanghai P. R. China"},{"name":"School of Materials Science and Engineering Tianjin University  Tianjin China"},{"name":"Hangzhou Institute of Medicine (HIM) Chinese Academy of Sciences Hangzhou  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanna","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical Biology, and Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, School of Medicine Shanghai Jiao Tong University  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1400-5040","authenticated-orcid":false,"given":"Ben","family":"Shi","sequence":"additional","affiliation":[{"name":"Hangzhou Institute of Medicine (HIM) Chinese Academy of Sciences Hangzhou  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical Biology, and Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, School of Medicine Shanghai Jiao Tong University  Shanghai P. R. 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