Designing multi-responsive polymeric amphiphiles with high molecular precision

Abstract: 

Comprehensive understanding of the moleucalr parameters that govern the ability of enzymes to degrade polymeric amphiphiles and their assemblies is crucial for the development of novel materials with tunable bio-degradation. One of the key challenges in the field is to study assembled polymeric nanoparticles in complex biological media with high degree of resolution. Such studies are essential to understand the stability and degradability of polymeric assemblies under conditions that mimics better the biological environment, which polymeric delivery platforms encounter upon administration into the body. 

   In the past few years, we designed and synthesized labeled amphiphilic PEG-dendron hybrids with enzymatically cleavable hydrophobic end-groups. The labeling of the amphiphiles exactly in the interface between the hydrophilic and hydrophobic blocks resulted in high degree of interactions between the labeling moieties, leading to different spectral properties of the labeled assemblies. Upon enzymatic hydrolysis and disassembly of the polymeric assemblies, the polymers diffuse away and the labeling groups can no longer interact and the polymers regain the intrinsic spectral properties of the labeling moieties. Taking advantage of the high molecular precision that emerges from using a  monodisperse hydrophobic dendritic block, we could study the effects of precise minor changes of the hydrophobic blocks on the stability and degradability of the polymeric assemblies. Our studies demonstrate that one of the key challenges in designing enzyme-responsive amphiphiles is to overcome the need of balancing between stability and responsiveness. We will present several molecular designs aimed at overcoming this challenge.

 

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