Ultrasound and Redox-Triggered Morphology Transitions of Supramolecular Self-assemblies with pH Responsiveness for Triple-Controlled Release

The realization of multistage-controlled drug delivery at the cell level through the morphology transitions of supramolecular self-assemblies (SSA) is still a challenge. Herein, successive morphology transitions of SSA with pH responsiveness were successfully achieved through the subsequent action of ultrasound and redox stimuli. Specifically, we first prepared noncovalently PEGylated spherical self-assemblies formed by host–guest-conjugated amphiphilic β-CD dimers. The functionalized PEG could be associated/disassociated onto the spherical self-assemblies by adjusting pH values of solutions. They could reassemble into branched self-assemblies induced by ultrasonication. Such branched self-assemblies could be further dissociated into second spherical self-assemblies under a redox stimulus. This morphology transition process was used to conduct triple-controlled targeted drug delivery and release in cancer cells. This work will be beneficial for the design of smart SSA for controlled release in vivo.