Stimuli-Sensitive Dextran Hydrogel Composited with Clickable Reaction-Based Aggregation-Induced Emission Micelles: A Carrier of Hydrophobic Drugs

Introducing hydrophobic microstructures into polymer hydrogels has been considered recently as an effective strategy to design multifunctional hydrogel-based carriers for hydrophobic drug delivery. Herein, fluorescent micelle-hydrogel composites by combining aggregation-induced emission (AIE)-active polyethylenimine (PEI) micelles into a dextran hydrogel matrix for improving the delivery of doxorubicin (DOX) are presented. A synthetic protocol based on the mercaptoacetic acid locking imine (MALI) reaction was explored to effectively modify the side-chains of alkylated polyethylenimine (PEI-C-12) with AIEgens (aldehyde-functionalized tetraphenylethene, TPE-CHO). DOX-loaded micelle nanoparticles with AIE fluorescent properties and fluorescence resonance energy transfer (FRET) phenomenon were obtained via the self-assembly of the resulting amphiphilic TPE-PEI-C-12 and then encapsulated into dextran hydrogels formed by the disulfide-containing Schiff base reaction. The stimuli-sensitive release of the DOX-loaded AEI micelles from the hydrogel matrix and the following DOX release via demicellization was finally investigated by in vitro release and cell-labeling studies. The above results suggest that the AIE micelle-hydrogel system can be considered as a valuable carrier of hydrophobic drugs with potential in intracellular imaging and drug release tracing, especially for local drug delivery.