Carbon monoxide (CO), one of the most important gaseous signaling molecules, exhibits remarkable potential for antiproliferative therapy. Although extensive studies have been carried out on CO-releasing polymeric vehicles, their intracellular targeting behavior remains insufficiently elucidated. Herein, we report the design of CO-releasing polymersomes surface-modified with triphenylphosphine (TPP) for mitochondrial targeting. We demonstrate that reactive oxygen species (ROS) can trigger CO release from the polymersomes, and that the mitochondria-targeted nanovehicles exhibit superior cytotoxicity against cancer cells compared with their nonfunctionalized counterparts. We anticipate that the incorporation of mitochondrial targeting into CO-releasing polymersome systems will provide a promising strategy for the development of advanced gas-releasing polymer carriers with potential applications in gas therapy.
Yang et al. (Sat,) studied this question.