Extracellular Vesicles Facilitate the Transportation of Nanoparticles within and between Cells for Enhanced Tumor Therapy.

The interaction between nanoparticles and cells is closely associated with the therapeutic effects of nanomedicine. Nanoparticles could be transported among cells, but the process-related mechanism remains to be further explored. In this study, it was found that endocytosed cationic polymer nanoparticles (cNPs) could be excreted in an extracellular vesicle (EV)-coated form (cNP@EVs). It was deduced that cNPs may pass through early endosomes, multivesicular bodies (MVBs), and autophagic MVBs within cells. Moreover, a high level of autophagy facilitated the exocytosis process. Since EVs were the effective vehicles for conveying biological information and substances, cNP@EVs were proved to be efficient forms for the intercellular transportation of nanoparticles and have the potential as efficient biomimetic drug delivery systems. These properties endowed cNP@EVs with deep penetration and enhanced antitumor activity. Our findings provided a proof-of-concept for understanding the transfer process of nanoparticles among cells and may help us to further utilize EV-mediated transportation of nanoparticles, therefore, expanding its clinical application.