Keynote
Design and synthesis of enzymatically degradable polymeric amphiphiles for biomedical applications

Deep understanding of the parameters that govern the ability of enzymes to degrade polymeric assemblies is critical for the development of biodegradable materials for applications ranging from controlled drug delivery systems to tissue engineering. The limited accessibility of enzymes to hydrophobic substrates that may be hidden inside hydrophobic domains has turned out to be one of the key parameters that determine enzymatic degradability. In the past several years, we designed and synthesized amphiphilic PEG-dendron hybrids with enzymatically cleavable hydrophobic end-groups and studied the enzymatic hydrolysis of the resulting polymeric assemblies. The high molecular precision that emerges from the monodispersity of the hydrophobic dendritic block, enabled us to show how precise minor changes of the hydrophobic blocks can significantly affect the stability of polymeric assemblies towards enzymatic degradation. Furthermore, we demonstrated that the micellar stability in serum can also dictates the internalization mechanism of the polymeric assemblies into living cells.

Our results strongly support the hypothesis that enzymes cannot reach the core of polymeric assemblies and instead they gain excess to the non-assembled monomers, which are in equilibrium with the polymeric assemblies. This equilibrium-based mechanism may explain the poor or lack of degradability that is often-observed for many polymeric assemblies. Based on our insights, we have recently started to study novel multi-responsive polymeric assemblies that can overcome the challenge of designing stable and yet enzymatically degradable polymeric assemblies.