A Biomimetic Polymer Magnetic Nanocarrier Polarizing Tumor-Associated Macrophages for Potentiating Immunotherapy
A Biomimetic Polymer Magnetic Nanocarrier Polarizing Tumor-Associated Macrophages for Potentiating Immunotherapy
复制标题
仿生聚合物磁性纳米载体极化肿瘤相关巨噬细胞，用于增强免疫治疗
DOI：
10.1002/smll.202003543
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发表时间：
2020-08-18
期刊：
影响因子：
13.3
通讯作者：
Zhou, Shaobing
中科院分区：
文献类型：
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作者：
Liu, Lingqiao;Wang, Yi;Zhou, Shaobing
抗肿瘤免疫治疗的进展通常受到肿瘤相关巨噬细胞（TAM）的限制，肿瘤相关巨噬细胞（TAM）在肿瘤微环境中占免疫抑制细胞的最高比例，并且TAM也可以通过调节M2样表型来逆转。本研究开发了一种具有选择性靶向和极化作用的磁性纳米载体，用于增强乳腺癌的免疫治疗。该纳米载体PLGA-ION-R837@M（PIR @ M）首先通过制备包封Fe（3）O（4）NPs和Toll样受体7（TLR 7）激动剂咪喹莫特（R837）的磁性聚合物纳米颗粒（NPs），其次通过在NPs表面上涂覆脂多糖（LPS）处理的巨噬细胞膜以靶向TAM来实现。在Fe（3）O（4）NPs和R837的协同作用下，PIR @ M的细胞内摄取可以极大地将TAM从M2表型转变为抗肿瘤M1表型。通过对信号通路mRNA表达的分析，深入研究了极化的相关机制。与以往报道不同的是，Fe 3 O 4纳米粒主要通过铁离子激活IRF 5信号通路，而不是通过活性氧诱导的NF-κ B B信号通路。在Fe（3）O（4）NPs和R837的组合中，通过TAMs的极化增强免疫治疗可以有效地增强抗癌效果。
The progress of antitumor immunotherapy is usually limited by tumor-associated macrophages (TAMs) that account for the highest proportion of immunosuppressive cells in the tumor microenvironment, and the TAMs can also be reversed by modulating the M2-like phenotype. Herein, a biomimetic polymer magnetic nanocarrier is developed with selectively targeting and polarizing TAMs for potentiating immunotherapy of breast cancer. This nanocarrier PLGA-ION-R837 @ M (PIR @ M) is achieved, first, by the fabrication of magnetic polymer nanoparticles (NPs) encapsulating Fe(3)O(4)NPs and Toll-like receptor 7 (TLR7) agonist imiquimod (R837) and, second, by the coating of the lipopolysaccharide (LPS)- treated macrophage membranes on the surface of the NPs for targeting TAMs. The intracellular uptake of the PIR @ M can greatly polarize TAMs from M2 to antitumor M1 phenotype with the synergy of Fe(3)O(4)NPs and R837. The relevant mechanism of the polarization is deeply studied through analyzing the mRNA expression of the signaling pathways. Different from previous reports, the polarization is ascribed to the fact that Fe(3)O(4)NPs mainly activate the IRF5 signaling pathway via iron ions instead of the reactive oxygen species-induced NF-kappa B signaling pathway. The anticancer effect can be effectively enhanced through potentiating immunotherapy by the polarization of the TAMs in the combination of Fe(3)O(4)NPs and R837.