Towards mitochondrial targeting for the treatment of Alzheimer's Disease

Abstract

Nanoparticles (NPs) have emerged as a promising approach to overcoming biological barriers imposed by the human body. Polymeric NPs offer a superior synthetic flexibility and advances in polymerization chemistries have made polymeric architectures with precisely tuned properties accessible. Ring opening metathesis polymerization (ROMP) has become a popular polymerization technique due to its mild conditions a tolerance to an array of functional groups. We successfully synthesized two generations of ROMP monomers that feature polymerizable group and a mitochondrial targeting ligand linked together via a hydrophilic spacer. This monomer can be co-polymerized with another ROMP monomer bearing a fluorescent molecule to enable the visualization of the polymeric NPs in the cell. The second-generation monomers differ from the first-generation analogues by their three-fold longer hydrophilic linkers. Co-polymers prepared from second-generation monomers show cellular up-take but no mitochondrial localization.