Affiliation:
1. School of Pharmacy Jiangsu Key Laboratory of Inflammation and Molecular Drug Targets Nantong University Nantong Jiangsu 226001 China
2. State Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and Protection and School for Radiological and Interdisciplinary Sciences (RAD‐X) Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions Soochow University Suzhou Jiangsu 215123 China
Abstract
AbstractCancer and its metastasis/recurrence still threaten human health, despite various advanced treatments being employed. 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‐STING stimulation capacity, is integrated with polyethylene glycol grafted poly (lactic‐co‐glycolic) acid co‐polymer (PLGA‐PEG), obtaining PLGA‐PEG/DMXAA (PPD) nanoparticles to induce the tumor‐specific 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‐mediated therapies could trigger potent systemic anti‐tumor immunity via inducing the immunogenic death of tumor cells and activating the cGAS‐STING pathway. Together with anti‐PD‐L1, PPD‐mediated 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‐loaded nano‐micelle could be utilized to enhance the therapeutic effect of multiple treatments for synergistic and systemic antitumor response, providing a practical strategy for cancer therapy.
Funder
National Natural Science Foundation of China
Subject
Biomaterials,Biotechnology,General Materials Science,General Chemistry
Cited by
1 articles.
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