Targeted doxorubicin-loaded mesenchymal stem cells-derived exosomes as a versatile platform for fighting against colorectal cancer

• Published in: Life sciences (1973) 2020-11, Vol.261, p.118369-118369, Article 118369
• Main Authors: Bagheri, Elnaz, Abnous, Khalil, Farzad, Sara Amel, Taghdisi, Seyed Mohammad, Ramezani, Mohammad, Alibolandi, Mona
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Aptamer; Aptamers; Biocompatibility; Cancer; Carboxylic acids; Colon; Colorectal carcinoma; Doxorubicin; Drug delivery; Electroporation; Encapsulation; Exosome, doxorubicin, MUC1; Exosomes; Flow cytometry; Fluoroscopic imaging; Immunogenicity; In vivo methods and tests; Intravenous administration; Mesenchymal stem cell (MSC); Mesenchymal stem cells; Stem cell transplantation; Stem cells; Targeted drug delivery; Tumors; Ultracentrifugation; Vesicles
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2020.118369

Exosomes hold great potential for cancer treatment to deliver therapeutics due to its inherent low immunogenicity. Exosomes are biocompatible cell-exocytosed secreted vesicles by most cell types, which can be used to construct novel biomanufacturing platform for drug delivery and cancer therapy. In this study, we implemented nano-sized vesicles which were secreted by mesenchymal stem cell (MSC), to encapsulate doxorubicin (DOX) through electroporation method (DOX@exosome). DOX was loaded into exosomes, with an encapsulation efficiency of up to 35% and separated by ultracentrifugation. Subsequently, carboxylic acid-end MUC1 aptamer was used to covalently decorate the surface amine groups of the exosomes via amide bond formation to provide selective guided drug delivery (DOX@exosome-apt). The data showed that the DOX@exosome-apt provided highly efficient DOX transportation to MUC1-positive cancer cells in vitro as confirmed by MTT and flow cytometry experiments. Moreover, in vivo study on ectopic model of C26 (mouse colon adenocarcinoma) in BALB/c mice indicated that the single dose intravenous injection of DOX@exosome-apt significantly suppress tumor growth in comparison with free DOX. Ex vivo fluorescent imaging also verified the desirable biodistribution of DOX@exosome-apt by exhibiting higher tumor accumulation and faster liver clearance in comparison with DOX@exosome and free DOX. It could be concluded that MUC1 aptamer-decorated exosomes can be implemented therapeutically for the safe and versatile delivery of DOX to colon adenocarcinoma, thus offering valuable platform for clinical applications. •We implemented membrane vesicles secreted by mesenchymal stem cell to encapsulate DOX.•DOX was loaded into exosomes, with an encapsulation efficiency of up to 35%.•MUC1 aptamer was covalently conjugated to the amine groups on the exosomes•Ex vivo fluorescent imaging also verified the desirable biodistribution.•The prepared system efficiently suppressed tumor growth in C26 tumor bearing mice.