Engineering macrophage-derived exosomes for targeted chemotherapy of triple-negative breast cancer

• Published in: Nanoscale Vol. 12; no. 19; pp. 1854 - 1862
• Main Authors: Li, Sha, Wu, Yijing, Ding, Fei, Yang, Jiapei, Li, Jing, Gao, Xihui, Zhang, Chuan, Feng, Jing
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 21.05.2020
• Subjects: Anticancer properties; Apoptosis; Biocompatibility; Blood circulation; Breast cancer; Cell Line, Tumor; Chemotherapy; Doxorubicin; Doxorubicin - pharmacology; Drug delivery systems; Exosomes; Glycolic acid; Humans; Immune system; In vivo methods and tests; Macrophages; Nanoparticles; Toxicity; Triple Negative Breast Neoplasms - drug therapy
• ISSN: 2040-3364; 2040-3372
• 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. A macrophage exosome coated nanoplatform for targeted chemotherapy of triple-negative breast cancer.