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However, current sequential delivery is mainly achieved through enzyme\u2010 or acid\u2010dependent degradation of the nanocarrier, which would be influenced by the heterogeneous tumor microenvironment, and unloading efficiency of the drug acting on the target outside tumor cells is usually unsatisfactory. Here, a light\u2010triggered sequential delivery strategy based on a liposomal formulation of doxorubicin (DOX)\u2010loaded small\u2010sized polymeric nanoparticles (DOX\u2010NP) and free sunitinib in the aqueous cavity, is developed. The liposomal membrane is doped with photosensitizer porphyrin\u2013phospholipid (PoP) and hybridized with red blood cell membrane to confer biomimetic features. Near\u2010infrared light\u2010induced membrane permeabilization triggers the \u201cultrafast\u201d and \u201cthorough\u201d release of sunitinib (100% release in 5\u00a0min) for antiangiogenic therapy and also myeloid\u2010derived suppressor cell (MDSC) inhibition to reverse the immunosuppressive tumor environment. Subsequently, the small\u2010sized DOX\u2010NP liberated from the liposomes is more easily uptaken by tumor cells for improved immunogenic chemotherapy. RNA sequencing and immune\u2010related assay indicates therapeutic immune enhancement. This light\u2010triggered sequential delivery strategy demonstrates the potency in cancer multimodal therapy against multiple targets in different spatial positions in tumor microenvironment.<\/jats:p>","DOI":"10.1002\/adma.202106682","type":"journal-article","created":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T22:19:15Z","timestamp":1641421155000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":77,"title":["Light\u2010Triggered Efficient Sequential Drug Delivery of Biomimetic Nanosystem for Multimodal Chemo\u2010, Antiangiogenic, and Anti\u2010MDSC Therapy in Melanoma"],"prefix":"10.1002","volume":"34","author":[{"given":"Xing","family":"Lai","sequence":"first","affiliation":[{"name":"Hongqiao International Institute of Medicine Tongren Hospital and State Key Laboratory of Oncogenes and Related Genes Department of Pharmacology and Chemical Biology Shanghai Jiao Tong University School of Medicine (SJTU\u2010SM)  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