Constructing Mitochondria-Targeted Carbon Monoxide (CO)-Releasing Polymersomes for Enhanced Cancer Cell Killing

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.