The effects of umbilical cord-derived macrophage exosomes loaded with cisplatin on the growth and drug resistance of ovarian cancer cells

Abstract

Objective: To assess the feasibility of an exosome-based drug delivery platform for the potent chemotherapeutic agent cisplatin to treat ovarian cancer.

Significance: Exosomes have recently been used as drug delivery vehicles because of their natural advantages. Platinum-resistant forms of ovarian cancer require novel drug delivery methods to improve patient outcomes.

Methods: We developed and compared different methods of loading exosomes released by mononuclear M1 and M2 macrophages from umbilical cord blood with cisplatin. We characterized the morphology, drug capacity, method of cellular entry, and antitumor efficacy of the exosomes in vitro.

Results: Disruption of the exosomal membrane by sonication facilitated a high loading efficiency. Importantly, incorporation of cisplatin into umbilical cord blood-derived M1 macrophage exosomes increased its cytotoxicity 3.3× in drug-resistant A2780/DDP cells and 1.4× in drug-sensitive A2780 cells over chemotherapy alone. Loading of cisplatin into M2 exosomes increased its cytotoxicity by nearly 1.7× in drug-resistant A2780/DDP cells and 1.4× in drug-sensitive A2780 cells.

Conclusions: We conclude that cisplatin-loaded M1 exosomes are potentially powerful new tools for the delivery of chemotherapeutics to treat cancers regardless of drug resistance.

Keywords:

• Ovarian cancer
• drug resistance
• exosome
• cisplatin
• umbilical cord blood
• macrophages

Acknowledgments

The authors thank Editage (www.editage.cn) for English language editing.

Declaration of interest

The authors report no conflict of interest.

Additional information

Funding

This study was supported by the National Science Foundation of China under Grant [81602278].