Engineering Macrophage-derived Exosomes for Targeted Paclitaxel Delivery to Pulmonary Metastases

exosomes

Exosomes have recently emerged as a promising drug delivery system with low immunogenicity, high biocompatibility, and high efficacy of delivery. Researchers at University of North Carolina at Chapel Hill demonstrated earlier that macrophage-derived exosomes (exo) loaded with a potent anticancer agent paclitaxel (PTX) represent a novel nanoformulation (exoPTX) that shows high anticancer efficacy in a mouse model of pulmonary metastases. They now report the manufacture of targeted exosome-based formulations with superior structure and therapeutic indices for systemic administration. Herein, they developed and optimized a formulation of PTX-loaded exosomes with incorporated aminoethylanisamide-polyethylene glycol (AA-PEG) vector moiety to target the sigma receptor, which is overexpressed by lung cancer cells. The AA-PEG-vectorized exosomes loaded with PTX (AA-PEG-exoPTX) possessed a high loading capacity, profound ability to accumulate in cancer cells upon systemic administration, and improved therapeutic outcomes. The combination of targeting ability with the biocompatibility of exosome-based drug formulations offers a powerful and novel delivery platform for anticancer therapy.

Kim MS, Haney MJ, Zhao Y, Yuan D, Deygen I, Klyachko NL, Kabanov AV, Batrakova EV. (2017) Engineering Macrophage-derived Exosomes for Targeted Paclitaxel Delivery to Pulmonary Metastases: in vitro and in vivo Evaluations. Nanomedicine (17)30178-8. Epub ahead of print]. [abstract]

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