Leveraging Macrophage-Mediated Cancer Immunotherapy via a Cascading Effect Induced by a Molecularly Imprinted Nanocoordinator.
Leveraging Macrophage-Mediated Cancer Immunotherapy via a Cascading Effect Induced by a Molecularly Imprinted Nanocoordinator.
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DOI：
10.1021/acsami.3c03950
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发表时间：
2023-06
影响因子：
9.5
通讯作者：
Shuxin Xu;Zikuan Gu;Haifeng Lu;Peixin Guan;Zhen Liu
中科院分区：
文献类型：
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作者：
Shuxin Xu;Zikuan Gu;Haifeng Lu;Peixin Guan;Zhen Liu
肿瘤相关巨噬细胞(TAMs)的重新编程已成为癌症免疫治疗的一种有前途的策略。靶向治疗集成多种功能，在不影响全身或组织驻留巨噬细胞的情况下，充分利用巨噬细胞的抗肿瘤免疫功能，是重新编程的关键。在这里，通过将分子印迹和纳米技术相结合，我们合理地设计和设计了一种前所未有的纳米协调器，用于靶向重塑TAMs，通过诱导级联效应来充分利用巨噬细胞的抗肿瘤效果。该纳米协调器具有磁性氧化铁纳米内核和唾液酸印迹外壳。静脉注射到全身循环中，纳米协调器可以在肿瘤部位快速积聚，以响应外部磁铁的作用。然后，通过与肿瘤细胞过度表达的唾液酸特异性结合，纳米协调器锚定在肿瘤部位，并延长保留时间。通过与纳米协调器的结合，肿瘤细胞被标记了异物，这促进了巨噬细胞的内在吞噬。随后，巨噬细胞摄取的纳米配基有效地促进了巨噬细胞向M1表型的极化，从而激活了巨噬细胞的免疫治疗效果。在级联效应的协同作用下，这种纳米协调器有效地利用TAMs进行巨噬细胞介导的免疫治疗。这项研究提供了新的靶向疗法，使我们能够在不影响正常组织的情况下，充分利用巨噬细胞的抗肿瘤免疫功能。
Reprogramming tumor-associated macrophages (TAMs) has emerged as a promising strategy in cancer immunotherapy. Targeted therapeutics integrating multiple functions to fully leverage the antitumor immune functions of macrophages without affecting systemic or tissue-resident macrophages are crucial for TAM reprogramming. Herein, by integrating molecular imprinting and nanotechnology, we rationally designed and engineered an unprecedented nanocoordinator for targeted remolding of TAMs to fully leverage the antitumor efficacy of macrophages by inducing a cascade effect. The nanocoordinator features a magnetic iron oxide nanoinner core and sialic acid-imprinted shell. Intravenously administered into systemic circulation, the nanocoordinator can rapidly accumulate at the tumor site in response to an external magnet. Then, by specifically binding to sialic acid overexpressed on tumor cells, the nanocoordinator anchors at the tumor site with prolonged retention time. Via binding with the nanocoordinator, tumor cells are tagged with a foreign substance, which promotes the intrinsic phagocytosis of macrophages. Subsequently, the nanocoordinator taken up by macrophages effectively promotes the polarization of macrophages toward the M1 phenotype, thus activating the immunotherapeutic efficacy of macrophages. Synergized by the cascade effect, this nanocoordinator effectively harnesses TAMs for macrophage-mediated immunotherapy. This study offers new TAM-targeted therapeutics that allows us to fully leverage the antitumor immune functions of macrophages without affecting the normal tissue.