Tumor Vascular Destruction and cGAS ‐STING Activation Induced by Single Drug‐Loaded Nano‐Micelles for Multiple Synergistic Therapies of Cancer

A vascular disruptor-loaded nano-micelle is prepared to mediate photothermal therapy, radiotherapy, starvation therapy, and immunotherapy of breast cancer via inducing tumor-specific vascular destruction. This treatment strategy, together with anti-PD-L1, could almost achieve complete elimination of primary, metastatic, and recurrent tumors. 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 a...
Source: Small - Category: Nanotechnology Authors: Tags: Research Article Source Type: research