Targeted delivery of miRNA 155 to tumor associated macrophages for tumor immunotherapy
Targeted delivery of miRNA 155 to tumor associated macrophages for tumor immunotherapy
复制标题
将 miRNA 155 靶向递送至肿瘤相关巨噬细胞以进行肿瘤免疫治疗
DOI：
10.1021/acs.molpharmaceut.9b00065
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发表时间：
2019
影响因子：
4.9
通讯作者：
Dawei Chen
中科院分区：
文献类型：
--
作者：
Xinlong Zang;Xiaoxu Zhang;Xiuli Zhao;Haiyang Hu;Mingxi Qiao;Yihui Deng;Dawei Chen
肿瘤相关巨噬细胞（Tumor associated macrophages, tam）是肿瘤微环境中的重要组成部分。它们具有免疫抑制作用，促进肿瘤进展。靶向tam并对其表型进行重编程可能是一种很有前途的策略，可以恢复抗肿瘤免疫反应。在这项研究中，我们开发了一种基于脂质包被的磷酸钙纳米颗粒（CaP/miR@pMNPs）的microRNA递送系统，该纳米颗粒含有共轭甘露糖，并用ph响应材料进行空间屏蔽。纳米载体可以响应肿瘤微环境的低pH值，并暴露甘露糖促进tam细胞内化。在荷瘤小鼠模型中，载体可以重新激活tam并重新编程其功能，逆转免疫抑制肿瘤微环境，抑制肿瘤生长。总之，重定向tam的极化是肿瘤免疫治疗的潜在治疗策略。
Tumor associated macrophages (TAMs) are important components residing in the tumor microenvironment. They are immunosuppressive and promote tumor progression. Targeting TAMs and reprogramming their phenotype may be a promising strategy that can restore antitumor immune responses. In this study, we developed a microRNA delivery system based on lipid-coated calcium phosphonate nanoparticles (CaP/miR@pMNPs) containing conjugated mannose and sterically shielded with a pH-responsive material. The nanocarrier could respond to the low pH in the tumor microenvironment and expose mannose to promote cellular internalization in TAMs. The carrier could reactivate TAMs and reprogram their functions, reverse the immunosuppressive tumor microenvironment, and inhibit tumor growth in a tumor-bearing mouse model. In summary, redirecting the polarization of TAMs is a potential therapeutic strategy for tumor immunotherapy.