ABSTRACT: Stimuli-responsive degradation (SRD) or cleavage of dynamic covalent bonds in response to external stimuli is a promising property in the development of polymer-based multifunctional nanomaterials. These nanomaterials are designed to degrade upon the cleavage of dynamic linkages in response to single or multi-stimuli, thus tuning lower critical solution temperature, controlling nanoparticle morphologies, fabricating highly-ordered nanopores, and enhancing controlled drug release.
Our current focus is the self-assembled nanocarriers as a broad choice of materials for targeted drug delivery. Exploring disulfide-thiol chemistry, our group has developed various strategies to synthesize novel micelles with disulfide linkages positioned at different single locations. Recently, we have focused on an effective SRD strategy that centers on the development of new intracellular nanocarriers having multiple stimuli-responsive cleavable linkages at multiple locations, as in the micellar core, in the interlayered corona, and at the interface between the hydrophobic core and corona (denoted as ML-MSRD strategy). This new strategy enables the investigation of structure-property relationship between morphological variance and stimuli-responsive degradation. Ultimately, the results enable the optimization of degradable micelles offering enhanced release inside diseased cells, particularly targeted cancer cells.