Self-Assembly of Enzyme-Responsive Amphiphilic Polymer-Dendron Hybrids into Micelles with Different Hydrophilic Shells

In the recent years, a lot of attention is directed towards the study and development of nano-sized carriers, which can encapsulate or covalently bind molecular cargo within their cores. One of the promising applications for these kinds of carriers is in the field of drug delivery. For this use, there is a need for nano-carriers that could disassemble on demand under specific conditions, causing the release of their molecular cargo at the designated target site. Typically, these kind of nano-carriers are formed by the self-assembly of amphiphilic block copolymers into micelles or vesicles in aqueous media. There are numerous examples for stimuli-responsive micelles and vesicles that disassemble due to changes in temperature, pH, light irradiation and recently enzymatic activation. Enzymes are very appealing trigger due to their catalytic nature, specificity and the fact that in many cases there is an overexpression of disease associated enzymes in diseased tissues. In previous works of our group we presented amphiphilic block copolymers based on hydrophilic PEG linked to a hydrophobic enzyme-responsive dendron. These PEG-dendron hybrids self-assembled in aqueous media into micelles, which disassembled after activation with specific enzyme. In this work, we expand the variety of hydrophilic polymers that can be used for the preparation of amphiphilic polymer-dendron hybrids. The effect of polymer composition and charge on the assembly and disassembly were thoroughly studied using various techniques. The results demonstrate the modularity of our synthetic design and open the way for enzyme-responsive polymeric micelles with adjustable hydrophilic shell and surface properties.