Construction of Nitric Oxide-Releasing Poly(trimethylene carbonate)-Based Polymersomes Equipped with Cell-Penetrating Guanidine

Nitric oxide (NO), one of the important gaseous signaling molecules, has shown great potential in treating many diseases. Thus, the construction of NO-releasing polymeric vehicles has garnered much attention. Despite the great effort made in the field, facilitating the internalization of polymer-based NO donors within cells remains a challenge. In this work, we reported a rational design of poly(trimethylenecarbonate) (PTMC)-based NO-releasing polymersomes equipped with cell-penetrating guanidine. The guanidine group conjugated with the polymersome significantly enhances the cellular uptake efficiency induced by the unique interactions between guanidine and the cancer cell surface. The in vitro studies demonstrated that light irradiation could trigger NO release from polymersomes, and the guanidine-functionalized polymersomes have superior cytotoxicity against cancer cells than unfunctionalized polymersomes. We expect that integrating cell-penetrating properties into NO-releasing polymersome systems provides a promising strategy for constructing advanced gas-releasing polymeric vehicles.