Targeted Delivery of Zoledronate To Tumor Associated Macrophages For Cancer Immunotherapy
Targeted Delivery of Zoledronate To Tumor Associated Macrophages For Cancer Immunotherapy
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唑来膦酸靶向递送至肿瘤相关巨噬细胞用于癌症免疫治疗
DOI：
10.1021/acs.molpharmaceut.9b00261
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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;Haiyang Hu;Mingxi Qiao;Xiuli Zhao;Yihui Deng;Dawei Chen
肿瘤相关巨噬细胞（TAM）由肿瘤衍生因子从循环单核细胞中募集，其分化为驻留在肿瘤微环境中的巨噬细胞。TAM在促进血管生成、侵袭、转移和免疫逃逸等方面发挥重要作用，直接去除TAM是肿瘤免疫治疗的一种有前景的策略。在这项研究中，我们开发了脂质涂层唑来膦酸钙纳米粒子（CaZol@ pMNP）含有共轭甘露糖，这是空间屏蔽与细胞外pH敏感材料。NPs特异性靶向TAM并在体外和体内诱导其凋亡。在S180荷瘤小鼠模型中，CaZol@ pMNP有效地消除了TAM，显著减少了血管生成，降低了免疫抑制，并最终抑制了肿瘤生长，而没有引起全身效应。收集的数据表明使用CaZol@ pMNP直接消耗TAM用于癌症免疫治疗的潜力。
Tumor-associated macrophages (TAMs) are recruited from circulatory monocytes by tumor-derived factors, which differentiate into macrophages residing in the tumor microenvironment. TAMs play critical roles in promoting angiogenesis, invasion, metastasis and immune escape, and the direct depletion of TAMs is a promising strategy for tumor immunotherapy. In this study, we developed lipid-coated calcium zoledronate nanoparticles (CaZol@pMNPs) containing conjugated mannose, which were sterically shielded with an extracellular pH-sensitive material. The NPs specifically targeted TAMs and induced their apoptosis in vitro and in vivo. In a S180 tumor-bearing mouse model, CaZol@pMNPs effectively depleted TAMs, markedly decreased angiogenesis, reduced immune suppression, and eventually restrained tumor growth without eliciting systemic effects. The collective data indicate the potential of the direct depletion of TAMs using CaZol@pMNPs for cancer immunotherapy.