Аннотация:Exosomes have recently come into focus as “natural nanoparticles” for use as drug delivery
vehicles. Our objective was to assess the feasibility of an exosome-based drug delivery platform
for a potent chemotherapeutic agent, paclitaxel (PTX), to treat MDR cancer. Herein, we
developed and compared different methods of loading exosomes released by macrophages with
PTX (exoPTX), and characterized their size, stability, drug release, and in vitro antitumor
efficacy. Reformation of the exosomal membrane upon sonication resulted in high loading
efficiency and sustained drug release. Importantly, incorporation of PTX into exosomes
increased cytotoxicity more than 50 times in drug resistant MDCKMDR1 (Pgp+) cells. Next, our
studies demonstrated a nearly complete co-localization of airway-delivered exosomes with
cancer cells in a model of murine Lewis Lung Carcinoma pulmonary metastases, and a potent
anticancer effect in this mouse model. We conclude that exoPTX holds significant potential for
the delivery of various chemotherapeutics to treat drug resistant cancers.