The importance of molecular precision in designing enzymatically degradable polymeric amphiphiles

תמונה_סמינרים
02.01.2020
14:30
David Wang Auditorium, 3rd floor Dalia Maydan Bldg.
Prof. Roey J. Amir

Prof. Roey J. Amir

School of Chemistry
Tel Aviv University

Deep understanding of the molecular parameters that control the enzymatic degradation of polymeric assemblies is critical for the rational design of biodegradable materials for applications ranging from tissue engineering to drug delivery systems. It is clear that one of the key features that determine the enzymatic degradability is the limited access of the enzyme to the hydrophobic substrates that are hidden inside the hydrophobic domains. In our group, we design amphiphilic PEG-dendron hybrids with enzymatically cleavable lipophilic end-groups and study their self-assembly and enzymatic hydrolysis. The monodispersity of the dendritic block, allows us to study how minor alternations of the hydrophobic dendrons affect the stability of the assemblies towards enzymatic degradation. Recently, in vitro cellular internalization studies for these assemblies demonstrate that the micellar stability in serum and internalization mechanism of the polymeric assemblies can be tuned by precisely adjusting the hydrophobicity of the hydrophobic block. The wide range of micellar stabilities, ranging from readily degradable to undegradable and the diverse internalization pathways due to minor changes in the hydrophobic block, highlight the important role that polydispersity might play in controlling micellar stability towards enzymatic degradation. Our mechanistic insights can explain the often-reported poor enzymatic degradability of many polymeric assemblies, which may limit their further development into clinically approved delivery vehicles.