Li Sha, Wu Yijing, Ding Fei, Yang Jiapei, Li Jing, Gao Xihui, Zhang Chuan, Feng Jing
Anhui University of Science and Technology Affiliated Fengxian Hospital, 6600 Nanfeng Road, Fengxian District, Shanghai, 201499, China and Medical College, Anhui University of Science and Technology, 168 Taifeng Road, Huainan, 232001, China.
Zhiyuan College, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China.
Nanoscale. 2020 May 21;12(19):10854-10862. doi: 10.1039/d0nr00523a.
Triple-negative breast cancer (TNBC) is the most metastatic and recurrent subtype of all breast cancers. Owing to the lack of therapeutic targets, chemotherapy and surgical intervention are the only treatments for TNBC. However, the effectiveness of chemotherapeutics is limited by its shortcomings such as poor targeting, easy removal and high toxicity. Recently, exosomes have attracted more and more attention as a drug delivery system. As endogenous vesicles, exosomes ensure low immunogenicity, nontoxicity, and long blood circulation time. In addition, immune cell-derived exosomes can mimic the immune cell to target tumor cells. Herein, we developed a macrophage-derived exosome-coated poly(lactic-co-glycolic acid) nanoplatform for targeted chemotherapy of TNBC. To further improve the tumor targetability, the surface of the exosome was modified with a peptide to target the mesenchymal-epithelial transition factor (c-Met), which is overexpressed by TNBC cells. The results showed that the engineered exosome-coated nanoparticles significantly improved the cellular uptake efficiency and the antitumor efficacy of doxorubicin. In vivo study demonstrated that the nanocarriers exhibited remarkable tumor-targeting efficacy, led to increased inhibition of tumor growth and induced intense tumor apoptosis. These results indicated that the engineered macrophage exosome-coated nanoparticles were a promising drug delivery strategy for TNBC treatment.
三阴性乳腺癌（TNBC）是所有乳腺癌中转移性和复发性最强的亚型。由于缺乏治疗靶点，化疗和手术干预是TNBC的唯一治疗方法。然而，化疗药物的有效性受到其靶向性差、易清除和高毒性等缺点的限制。近年来，外泌体作为一种药物递送系统越来越受到关注。作为内源性囊泡，外泌体具有低免疫原性、无毒性和长血液循环时间的特点。此外，免疫细胞衍生的外泌体可以模拟免疫细胞靶向肿瘤细胞。在此，我们开发了一种巨噬细胞衍生的外泌体包被的聚乳酸-羟基乙酸纳米平台用于TNBC的靶向化疗。为了进一步提高肿瘤靶向性，外泌体表面用一种靶向间充质上皮转化因子（c-Met）的肽进行修饰，c-Met在TNBC细胞中过表达。结果表明，工程化的外泌体包被纳米颗粒显著提高了阿霉素的细胞摄取效率和抗肿瘤疗效。体内研究表明，纳米载体表现出显著的肿瘤靶向疗效，导致肿瘤生长抑制增加并诱导强烈的肿瘤细胞凋亡。这些结果表明，工程化的巨噬细胞外泌体包被纳米颗粒是一种有前途的TNBC治疗药物递送策略。
