Abstract 2590: Nano-exosomes with miRNA: A new therapeutic approach

Access to reliable and effective therapeutics for patients suffering from aggressive triple-negative breast cancer (TNBC) has been clinically challenging to achieve due to lack of targetable mutations and high heterogeneity in the tumor cells. Therapeutic approaches to reduce mortality in the TNBC patient subset requires an innovative and targeted approach to drug delivery, which is presented here in the form of labeled-exosomes. In this study, we have developed a novel method to bioengineer exosomes, where an antibody is covalently bonded to a fatty acid, which is then anchored into the exosomal membrane to create labeled-exosomes. Our data demonstrate that labeled-exosomes can contain up to 700,000-fold higher miRNA concentrations and can deliver miRNA cargo with increased efficiency into MDA-MB-231 TNBC cells. Results further reveal that insertion of a specific antibody-label to the exosomal membrane significantly increases microRNA uptake into MDA-MB-231 cells, and is further enhanced in cells overexpressing that same antibody marker on their surface. The customizable bioengineering of the labeled-exosomes makes it a highly versatile tool to target cells based on surface marker expression and increase miRNA or other therapeutic cargo delivery. Most importantly, the relevancy of this model reaches far beyond its success in just TNBC cells and can also be translated to several different disease models that require specific targeting with an encapsulated miRNA or therapeutic. We believe this is a novel and exciting utilization of exosomes with a high degree of customization based on surface markers on the target cell, as well as microRNA cargo loaded into the exosome to inhibit a specific oncogene. Citation Format: Sudeepti Kuppa, Balazs Rada, Arthur Roberts, Mandi M. Murph. Nano-exosomes with miRNA: A new therapeutic approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2590.