Ultrasound-responsive polymersomes capable of endosomal escape for efficient cancer therapy

Stimuli-responsive anticancer drug delivery vehicles have attracted increasing attention in nanomedicine. However, controlled drug release in vivo is still an important challenge, as traditional stimuli lack maneuverability. To solve this problem, we designed an ultrasound and pH-responsive polymersome by self-assembly of poly(ethylene oxide)-block-poly(2-(diethylamino)ethyl methacrylate)-stat-poly(methoxyethyl methacrylate) [PEO-b-P(DEA-stat-MEMA)], where PEO acts as the corona-forming block, DEA acts as the endosomal escape segment, and MEMA acts as the ultrasound-responsive segment. This strategy combines the advantages of noninvasive ultrasonic stimulus which can be applied from outside to any organ regardless of depth, and the weakly acidic microenvironment of tumor tissue. In vitro experiments confirmed excellent endosomal escape ability, on-demand drug release behavior, low cytotoxicity, and high intracellular delivery efficiency of polymersomes. In vivo antitumor tests revealed that in the presence of sonication, the anticancer drug was released at an accelerated rate from these ultrasound-responsive polymersomes, and the DOX-loaded polymersomes + sonication group significantly inhibited tumor growth (95% reduction in tumor mass) without any side effects. Overall, this ultrasound-responsive polymersome provides us with a fresh insight into designing next-generation stimuli-responsive drug carriers with better maneuverability and higher chemotherapeutic efficiency.