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Apart from surgery, photodynamic therapy (PDT) is perceived as another capable method for the treatment of oral cancer. However, limited oxygen content of tumor microenvironment decreased the efficiency of current PDT. Hence, a complementary tumor\u2010killing system is developed to overcome PDT\u2010induced oxygen depletion by introducing hypoxia\u2010activated chemotherapy drugs into tumor\u2010targeting liposomes. First, liposomes derived from red blood cell (RBC) membrane are decorated with tumor\u2010targeting formic acid (FA) and designed to carrying photosensitizer TPP and the hypoxia\u2010activated drug TPZ (<jats:bold>TPZ\/TPP@RBC\u2010FA<\/jats:bold>). Laser irradiation on tumor initiated the discharge of chemotherapeutic drugs (TPZ) from <jats:bold>TPZ\/TPP@RBC\u2010FA<\/jats:bold> liposomes by increasing the reactive oxygen species, causing the aggravated intratumoral hypoxia and the further generation of the toxic TPZ radicals. The combination of hypoxia\u2010activated chemotherapy and photodynamic therapy will not only induced efficient cell apoptosis but also caused immunogenic cell death and immunocyte activation. The strategy of loading drugs into liposomes also demonstrated acceptable biosafety. It is believed that the strategy of combining of photodynamic therapy and hypoxia\u2010activated chemotherapy with liposomes can be implemented for the oral cancer treatment in the near future.<\/jats:p>","DOI":"10.1002\/adhm.202404395","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T06:25:07Z","timestamp":1739514307000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Hypoxia\u2010Activated Liposomes Enable Synergistic Photodynamic Therapy for Oral Cancer"],"prefix":"10.1002","volume":"14","author":[{"given":"Jiaxuan","family":"Chen","sequence":"first","affiliation":[{"name":"Cancer Institute Xuzhou Medical University  209 Tongshan Road Xuzhou Jiangsu 221004 China"},{"name":"Center of Clinical Oncology The Affiliated Hospital of Xuzhou Medical University  99 Huaihai Road Xuzhou Jiangsu 221002 China"},{"name":"Jiangsu Center for the Collaboration and Innovation of Cancer 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