Azobenzene-Based Cross-Linked Small-Molecule Vesicles for Precise Oxidative Damage Treatments Featuring Controlled and Prompt Molecular Release

Precise therapy has become prevalent in clinical practice owing to its accurate and efficient targeting treatment of diseases. Such treatments involving polymersomes as carriers have great potential to lesion sites without damage to normal tissues. However, due to the inherent thick hydrophobic layer of polymersomes, an instantaneous release response to external stimuli remains a challenge. To tackle this challenge, here, we report on the synthesis and applications of azobenzene-containing photochromic vesicles as delivery vectors. These vesicles are assembled from small-molecule amphiphiles that have been developed to provide a fast response and promote instantaneous release due to molecular size reduction compared with macromolecular polymersomes. After cross-linking, the stability of vesicles under a physiological environment is notably enhanced. By varying UV and visible light irradiation, the “gate” of vesicles can be opened and closed reversibly for the controlled release of capsuled cargoes. In vitro experiments display that the vesicles can be applied to load cysteamine for eliminating excess reactive oxygen. The synthesized vesicles here show high performance in controlled and instantaneous release in cells both in time and space. By our approach, oxidative damage to cellular biomolecules can be substantially reduced.