Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300192, P.R. China.
Adv Sci (Weinh). 2023 May;10(15):e2207456. doi: 10.1002/advs.202207456. Epub 2023 Mar 26.
The regulation of tumor immunosuppressive microenvironments via precise drug delivery is a promising strategy for preventing tumor recurrence and metastasis. Inspired by the stealth strategy, a stealthy nanovehicle based on neutrophil camouflage is developed to achieve precise delivery and tumor immunotherapy by triggering pyroptosis. The nanovehicle comprises anti-CD11b- and IR820-conjugated bovine serum albumin nanoparticles loaded with decitabine. Camouflaged by neutrophils, the nanovehicles achieve efficient tumor delivery by neutrophil hitchhiking owing to the biotropism of neutrophils for tumors. The fluorescent signal molecule, IR820, on the nanovehicle acts as a navigation monitor to track the precise delivery of the nanovehicle. The released decitabine upregulates gasdermin E, and laser irradiation activates caspase-3, thereby resulting in pyroptosis, which improves the system's adaptive immune response. In a triple-negative breast cancer animal model, it regulates the immunosuppressive microenvironment for effective tumor immunotherapy and induces a long-lasting and strong immune memory to prevent lung metastasis.
通过精确的药物传递来调节肿瘤免疫抑制微环境是预防肿瘤复发和转移的一种有前途的策略。受伪装策略的启发，开发了一种基于中性粒细胞伪装的隐形纳米载体，通过触发细胞焦亡来实现精确的递药和肿瘤免疫治疗。该纳米载体由载有地西他滨的抗 CD11b 和 IR820 偶联牛血清白蛋白纳米颗粒组成。由于中性粒细胞对肿瘤的嗜性，纳米载体被中性粒细胞伪装后，能够通过中性粒细胞搭便车实现高效的肿瘤递送。纳米载体上的荧光信号分子 IR820 充当导航监测器，以跟踪纳米载体的精确递送。释放的地西他滨上调了 GSDME，激光照射激活了 caspase-3，从而导致细胞焦亡，这提高了系统的适应性免疫反应。在三阴性乳腺癌动物模型中，它调节了免疫抑制微环境，实现了有效的肿瘤免疫治疗，并诱导了持久而强烈的免疫记忆，以防止肺转移。
