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Herein, a disulfide bond linked homodimer, Cy1280, which is modulated by albumin to accurately balance the fluorescence and ROS generation and exhibit a weak fluorescence and sealed PDT effect during blood circulation, is exploited. Cy1280 can be specifically internalized and dispersed at the tumor site via Organic Anion Transporter Proteins (OATPs) and thiol\u2010disulfide exchange mediated synergistic uptake and activated after mild sunlight irradiation (100 \u00b1\u00a05 Klx) to sensitize neighboring oxygen in cellular mitochondria to execute direct protein dysfunction effect. The dynamic covalent chemistry (DCC) facilitates prolonged and sustained retention in tumors (&gt;336 h) and demonstrates the efficacy of imaging\u2010guided solid\u2010tumor therapy in tumor\u2010bearing BALB\/C mice. This study resolves the inevitable stubborn impotent tumor penetration caused by bulky\u2010sized nanoparticles and high interstitial pressure of tumor with synergistic uptake manner, the long\u2010term circulation and sealed PDT manipulated with albumin also improve the whole body phototoxic symptom. The advantageous feature of Cy1280 provides a promising candidate for overcoming the off\u2010target phototoxicity and inadequate accumulation challenges in clinical translation with photosensitizers (PSs).<\/jats:p>","DOI":"10.1002\/smll.202411736","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T06:31:08Z","timestamp":1742193068000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Albumin Modulated Homodimer as an Efficient Photosensitizer for Long\u2010Term Imaging\u2010Guided Tumor Therapy Directed with Sunlight Irradiation"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1499-8759","authenticated-orcid":false,"given":"Zan","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical Engineering Nanjing University  Nanjing 210023 P. R. 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