An Intelligent Nanovehicle Armed with Multifunctional Navigation for Precise Delivery of Toll-Like Receptor 7/8 Agonist and Immunogenic Cell Death Amplifiers to Eliminate Solid Tumors and Trigger Durable Antitumor Immunity
An Intelligent Nanovehicle Armed with Multifunctional Navigation for Precise Delivery of Toll-Like Receptor 7/8 Agonist and Immunogenic Cell Death Amplifiers to Eliminate Solid Tumors and Trigger Durable Antitumor Immunity
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DOI：
10.1002/adhm.202102739
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发表时间：
2022-04-03
影响因子：
10
通讯作者：
Zhang, Zhiyue
中科院分区：
文献类型：
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作者：
Hao, Yanyun;Li, Hui;Zhang, Zhiyue
癌症免疫治疗在肿瘤学和血液学领域是革命性的。然而，由于T淋巴细胞浸润不足和免疫治疗药物的递送效率低，低应答率限制了该疗法的临床效益。本文设计了一种具有多功能导航功能的智能纳米载体(叶酸(FA)/1-（4-（氨基甲基）苄基）-2-丁基- 1h -咪唑[4,5-c]喹啉-4-胺（IMDQ)-奥沙利铂（F/IMO）@ cu），分别用于向肿瘤细胞和树突状细胞（DCs）精确递送货物。纳米载体是基于近红外响应的无机cu纳米颗粒，作为光敏剂和化疗药物奥沙利铂的载体，由于肿瘤内注射时cu表面存在叶酸而进入肿瘤细胞。此外，将toll样受体（TLR） 7/8激动剂偶联聚合物固定在CuS表面，用甘露糖修饰，使其在肿瘤微环境中与DCs结合。在激光照射下，纳米载体分解，释放奥沙利铂，消融肿瘤细胞，放大免疫原性细胞死亡，并结合光热疗法。甘露糖修饰的聚合物- tlr7 /8激动剂偶联物随后暴露，导致DCs的激活和T细胞的增殖。总的来说，这些智能纳米载体减轻了肿瘤负担，发挥了强大的抗肿瘤免疫反应，并产生了长期的免疫保护，以防止肿瘤复发。
Cancer immunotherapy is revolutionary in oncology and hematology. However, a low response rate restricts the clinical benefits of this therapy owing to inadequate T lymphocyte infiltration and low delivery efficiency of immunotherapeutic drugs. Herein, an intelligent nanovehicle (folic acid (FA)/1-(4-(aminomethyl) benzyl)-2-butyl-1H-imidazo[4,5-c]quinolin-4-amine (IMDQ)-oxaliplatin (F/IMO)@CuS) armed with multifunctional navigation is designed for the accurate delivery of cargoes to tumor cells and dendritic cells (DCs), respectively. The nanovehicle is based on a near infrared-responsive inorganic CuS nanoparticles, acting as a photosensitizer and carrier of the chemotherapeutic agent oxaliplatin, and enters tumor cells owing to the presence of folic acid on the surface of CuS upon intratumoral injection. Furthermore, a toll-like receptor (TLR) 7/8 agonist-conjugated polymer, anchored on the surface of CuS, is modified with mannose to bind with DCs in the tumor microenvironment. Upon exposure to laser irradiation, nanovehicles disassemble, releasing oxaliplatin, to ablate tumor cells and amplify immunogenic cell death in combination with photothermal therapy. Mannose-modified polymer-TLR7/8 agonist conjugates are subsequently exposed, leading to the activation of DCs and proliferation of T cells. Collectively, these intelligent nanovehicles reduce tumor burden, exert a robust antitumor immune response, and generate long-term immune protection to prevent tumor recurrence.