Supramolecular polymersomes constructed from water-soluble pillar[5]arene and cationic poly(glutamamide)s and their applications in targeted anticancer drug delivery

The development of smart and targeted drug delivery systems has promising potential to revolutionize cancer chemotherapy. Herein, supramolecular polymersomes were constructed using biocompatible water-soluble pillar[5]arene (WP5) and cationic poly(glutamamide)s (polymer 1) with good biodegradability. Based on the host–guest complexation between WP5 and butyl-ammonium groups on polymer 1, stable supramolecular macromolecular amphiphiles were obtained, which could self-assemble into supramolecular polymersomes. Furthermore, the generated polymersomes were able to encapsulate the hydrophilic anticancer drug mitoxantrone (MTZ) to achieve MTZ-loaded polymersomes. Importantly, decorated with biotin ligands on the surface, these polymersomes exhibited good targeting ability to deliver MTZ specifically to biotin receptor-positive cancer cells. After internalization into cancer cells, the loaded MTZ was released efficiently triggered by the acidic environment-induced polymersome disassembly. Moreover, MTZ-loaded polymersomes with targeting ligands on their surface could not only enhance the anticancer efficiency of MTZ but also effectively reduce the undesirable side effects on normal cells. The present work provides a novel strategy for the construction of smart supramolecular polymersomes, which may hold potential biomedical applications in targeted drug delivery.