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It is considered that ferroptosis provides a promising therapeutic strategy for optimizing oncotherapy. Although erastin is an effective ferroptosis trigger, the potential of its clinical application is largely restricted by its poor water solubility and concomitant limitations. To address this issue, an innovative nanoplatform (PE@PTGA) that integrated protoporphyrin IX (PpIX) and erastin coated with amphiphilic polymers (PTGA) to evoke ferroptosis and apoptosis is constructed and exemplified using an orthotopic hepatocellular carcinoma (HCC) xenograft mouse model as a paradigm. The self\u2010assembled nanoparticles can enter HCC cells and release PpIX and erastin. With light stimulation, PpIX exerts hyperthermia and reactive oxygen species to inhibit the proliferation of HCC cells. Besides, the accumulated reactive oxygen species (ROS) can further promote erastin\u2010induced ferroptosis in HCC cells. In vitro and in vivo studies reveal that PE@PTGA synergistically inhibits tumor development by stimulating both ferroptosis\u2010 and apoptosis\u2010related pathways. Moreover, PE@PTGA has low toxicity and satisfactory biocompatibility, suggesting its promising clinical benefit in cancer treatments.<\/jats:p>","DOI":"10.1002\/adhm.202301133","type":"journal-article","created":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T13:46:57Z","timestamp":1686664017000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Synergistic Photochemo Effects Based on Light\u2010Activatable Dual Prodrug Nanoparticles for Effective Cancer Therapy"],"prefix":"10.1002","volume":"12","author":[{"given":"Zhi\u2010Yong","family":"Liu","sequence":"first","affiliation":[{"name":"School of Materials and Chemistry Institute of Bismuth Science Shanghai Collaborative Innovation Center of Energy Therapy for Tumors University of Shanghai for Science and Technology  Shanghai 200093 China"},{"name":"Department of Gastroenterology and Hepatology and Shanghai Institute of Liver Diseases Zhongshan Hospital Fudan 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