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.
Keywords: endocytosis; extracellular vesicles; intercellular transportation; nanoparticles; penetration.