ENZYME-RESPONSIVE POLYMERIC MICELLES AS A PLATFORM FOR CONTROLLED DELIVERY

Stimuli-responsive amphiphilic block copolymers have attracted considerable attention in recent years due to their ability to self-assemble in aqueous media into nano-sized polymeric micelles. Such micelles can encapsulate within their hydrophobic cores small guest molecules (e. g. hydrophobic drugs or dyes) and release them on cue. Therefore, polymeric micelles are interesting candidates to act as nanocarriers for controlled delivery and in vivo diagnostics. To this end, there have been many reports of polymeric micelles that can respond to various types of stimuli such as pH, irradiated light, temperature or their combinations. However, polymeric micelles that can respond to variations in enzymatic activity are not as prominent in the literature. Utilization of enzymes as triggers for micellar disassembly might be considerably advantageous due to the catalytic efficiency and high selectivity of the activating enzymes towards their substrates. Furthermore, common occurring imbalances in enzymatic activities are often associated with many diseases, and may be picked up by cleverly designed polymeric micelles to induce a site-specific release of molecular payload. Our research group has recently developed an innovative and simple synthetic approach for preparation of amphiphilic PEG-dendron hybrids, which can self-assemble in aqueous media into enzyme-responsive polymeric micelles. Here we demonstrate how each part of the hybrid can be adjusted to tune the stability of the formed micelles and their disassembly rates in response to the enzymatic trigger. This approach might assist in future design of enzyme-responsive platforms for controlled delivery of poorly soluble drugs.