Photo- and pH- dually-responsive β-cyclodextrin-based supramolecular prodrug complexes self-assemblies for programmed drug delivery.

Despite the progress has been made in the application of supramolecular prodrug self-assemblies to enhance the functionality of drug delivery systems, the corresponding research on multiple responsive supramolecular prodrug self-assemblies for programmed drug delivery is still limited. In this paper, the synthesis and self-assembly behaviours of supramolecular prodrug complexes (SPCs) with β-cyclodextrin-acylhydrazone-DOX and the targeting of azobenzene-terminated poly(2-(dimethylamino)ethyl methacrylate) (Azo-PDMA-FA) as building blocks are investigated and described. The obtained SPCs can further form self-assemblies based on their amphiphilic nature. Next, SPCs-based multi-compartment vesicles and complex micelles, which are confirmed by transmission electron microscopy (TEM) and dynamic/static light scattering (DLS/SLS), are obtained with good reversibility under alternative visible light or UV irradiation. Furthermore, three-stage programmed drug delivery behaviour was observed from dually responsive SPCs-based self-assemblies utilizing UV and pH stimuli. Specifically, SPCs first self-assembled into multi-compartment vesicles accompanied by a slow release of DOX. Next, UV light irradiation induced the dissociation of β-CD/Azo, leading to the morphology transition and slightly enhanced release of DOX. When the self-assemblies were transferred to PBS solution (pH 5.0), the release rates increased notably due to the broken acylhydrazone bond. Finally, basic cell experiments further demonstrated that the SPCs-based self-assemblies could be internalized into cancer cells, suggesting their promise for applications in cancer therapy.