Extracellular vesicles containing fullerene derivatives prepared by an exchange reaction for photodynamic therapy.

Extracellular vesicles (EVs) have excellent biocompatibility and long retention times in the circulation and have consequently been expected to be useful as drug-delivery systems. However, their applications have been limited because of the inability to introduce hydrophobic compounds to EVs without the use of harmful organic solvents. Herein, we developed an organic-solvent-free drug-loading technique based on the host exchange reaction. We demonstrated that the exchange reaction enabled quantitative loading of EVs with highly concentrated (0.1 mM) hydrophobic fullerene derivatives. Fullerene derivative-loaded EVs (EVs/C60) could eliminate cancer cell lines more efficiently than fullerene derivative-loaded liposomes (Lip/C60). Moreover, the photodynamic activity of EVs/C60 was fivefold higher than that of the clinically available photosensitizer photofrin. EVs/C60 could efficiently suppress tumor growth in tumor-xenograft model mice.