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通过甘露糖化混合胶束靶向递送达沙替尼以耗尽肿瘤相关巨噬细胞用于肿瘤免疫治疗。

Targeted Delivery of Dasatinib to Deplete Tumor-Associated Macrophages by Mannosylated Mixed Micelles for Tumor Immunotherapy.

机构信息

School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016 PR China.

School of Basic Medicine, Qingdao University, Ningxia Road 308, Qingdao 266071, PR China.

出版信息

ACS Biomater Sci Eng. 2020 Oct 12;6(10):5675-5684. doi: 10.1021/acsbiomaterials.0c01046. Epub 2020 Sep 16.

Abstract

Tumor-associated macrophages (TAMs) are abundant in tumors and predominately show protumor M2-type fostering tumor progression. Specific depletion of TAMs is conceivably favorable for antitumor therapy. In this study, mannosylated mixed micelles (DAS-MMic) were developed to specifically deliver dasatinib (DAS) to eliminate TAMs for tumor immunotherapy. In vitro and in vivo results showed that DAS-MMic could effectively eradicate TAMs, decrease angiogenesis, reprogram the immunosuppressive tumor microenvironment, and finally suppress tumor progression. These data suggest the potential of direct elimination of TAMs by DAS-MMic for tumor immunotherapy.

摘要

肿瘤相关巨噬细胞(TAMs)在肿瘤中大量存在,主要表现为促进肿瘤进展的 M2 型。特异性耗尽 TAMs 可能有利于抗肿瘤治疗。在这项研究中,制备了甘露糖化混合胶束(DAS-MMic)以特异性递送达沙替尼(DAS)来消除 TAMs 用于肿瘤免疫治疗。体外和体内结果表明,DAS-MMic 可以有效清除 TAMs,减少血管生成,重塑免疫抑制性肿瘤微环境,最终抑制肿瘤进展。这些数据表明,DAS-MMic 通过直接消除 TAMs 用于肿瘤免疫治疗的潜力。

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