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It is of great significance to develop simple drug formulations to enhance the efficacy and synergistic integration of various monotherapies. Herein, DMXAA, a vasodestructive agent with cGAS\u2010STING stimulation capacity, is integrated with polyethylene glycol grafted poly (lactic\u2010<jats:italic>co<\/jats:italic>\u2010glycolic) acid co\u2010polymer (PLGA\u2010PEG), obtaining PLGA\u2010PEG\/DMXAA (PPD) nanoparticles to induce the tumor\u2010specific vascular destruction for multiple synergistic therapies of cancer. PPD could induce the formation of blood clots in the tumor after intravenous injection, which subsequently mediate photothermal therapy and further promote the release of oxygen for enhanced radiotherapy. Meanwhile, the enhanced vascular injury can induce perfect starvation therapy of tumor. More importantly, PPD\u2010mediated therapies could trigger potent systemic anti\u2010tumor immunity via inducing the immunogenic death of tumor cells and activating the cGAS\u2010STING pathway. Together with anti\u2010PD\u2010L1, PPD\u2010mediated therapies could not only remove the primary tumors, but also effectively eliminate the distant tumors, metastasis, and recurrence. Therefore, the modulation of tumor composition induced by a single drug\u2010loaded nano\u2010micelle could be utilized to enhance the therapeutic effect of multiple treatments for synergistic and systemic antitumor response, providing a practical strategy for cancer therapy.<\/jats:p>","DOI":"10.1002\/smll.202303517","type":"journal-article","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T05:53:43Z","timestamp":1689918823000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Tumor Vascular Destruction and cGAS\u2010STING Activation Induced by Single Drug\u2010Loaded Nano\u2010Micelles for Multiple Synergistic Therapies of Cancer"],"prefix":"10.1002","volume":"19","author":[{"given":"Jingyu","family":"Gu","sequence":"first","affiliation":[{"name":"School of Pharmacy Jiangsu Key Laboratory of Inflammation and Molecular Drug Targets Nantong University  Nantong Jiangsu 226001 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