Fujian Provincial Key Laboratory of Transplant Biology, Laboratory of Basic Medicine, 900th Hospital of the Joint Logistics Team, Fuzhou 350025, China.
Department of Pharmacy, 900th Hospital of the Joint Logistics Team, Fuzhou 350025, China.
Biomed Pharmacother. 2024 Sep;178:117220. doi: 10.1016/j.biopha.2024.117220. Epub 2024 Aug 1.
Immunotherapy has captured attention for its high clinical efficacy. However, its efficacy is limited by inadequate immune activation. Therefore, a platform to activate the immune system and amplify the host's immune response against tumors is urgently needed. Herein, a self-delivery photodynamic nanodrug (VAC@HSA) is reported as inducing immunogenic cell death (ICD), promoting the recruitment of dendritic cells (DCs), and normalizing tumor blood vessels. Firstly, verteporfin with laser assistance releases tumor-associated antigen to induce ICD, while celecoxib downregulates prostaglandin E2 and releases CCL5 to activate DC recruitment. Moreover, vasculature is normalized through axitinib, which contributes to reducing tumor hypoxia and reversing the immunosuppressive effects of vascular endothelial growth factor. This joint action promotes the infiltration of immune effector cells into the tumor. Therefore, the amplified photodynamic nanodrug with excellent biocompatibility effectively inhibits tumor growth and lung metastasis and produces a cascade of immune responses. Our study demonstrates a practically innovative strategy for activating cancer immunotherapy, which can alter the "cold" properties of tumors.
免疫疗法因其高临床疗效而备受关注。然而，其疗效受到免疫激活不足的限制。因此，迫切需要一个能够激活免疫系统并放大宿主对肿瘤免疫反应的平台。在此，报告了一种自递送光动力纳米药物（VAC@HSA），它可以诱导免疫原性细胞死亡（ICD），促进树突状细胞（DC）的募集，并使肿瘤血管正常化。首先，在激光辅助下，维替泊芬释放肿瘤相关抗原以诱导 ICD，而塞来昔布通过下调前列腺素 E2 并释放 CCL5 来激活 DC 募集。此外，通过阿昔替尼使血管正常化，有助于减少肿瘤缺氧并逆转血管内皮生长因子的免疫抑制作用。这种联合作用促进了免疫效应细胞浸润肿瘤。因此，具有优异生物相容性的放大光动力纳米药物有效地抑制肿瘤生长和肺转移，并产生级联免疫反应。我们的研究展示了一种用于激活癌症免疫疗法的创新策略，它可以改变肿瘤的“冷”特性。
