Enhancing the Stability and Selectivity of Nanocarriers by Dimerization of their Building Blocks

Enzyme-responsive micelles have a great potential as drug delivery systems due to the high selectivity and overexpression of disease-associated enzymes. Recently we have reported on enzyme-responsive amphiphilic block copolymers composed of a hydrophilic PEG block and a dendron with enzymatically cleavable lipophilic end-groups as the hydrophobic block. These amphiphilic hybrids formed micellar structures in aqueous environment and enzymatic activation led to their disassembly. However, when examining micelles and their properties, it is clear that one of the biggest challenges is the the risk of their fast dilution and disassembly in the body. By cross-linking the micelles we can increase their stability and decrease their spontaneous disassembly in the body. By choosing a reversible cross-linker such as disulfide bonds, we will also benefit the introduction of another stimuli-responsive group. This will open the way for smart nanocarriers with improved micellar stabilities that require activation by both types of stimuli for their disassembly.

Keywords:

Block copolymer micelles, Enzyme responsive materials, Nanocarriers.