Tuning Polymeric Nanoparticles for Efficient Gene Delivery

Bijay Singh, Ph.D.

Postdoctoral Research Associate, Northeastern University

Tuning Polymeric Nanoparticles for Efficient Gene Delivery

Polymeric nanoparticles for gene delivery can enter the cells through different endocytic pathways and get trapped in endosomes. Hence, the release of DNA from endosomes, that is, endosomal escape prior to their degradation in lysosomes, appears to be a major bottleneck determining the final efficiency of gene delivery. According to proton sponge hypothesis, polymer like polyethylenimine (PEI), due its high buffering capacity, induces endosomal escape through an osmotic burst of endosome thereby releasing the DNA into the cytoplasm. Here, the goal of our study is to design the optimal gene delivery vehicles by tuning the buffering capacity of PEI with glycerol molecules, and the role of buffering capacity of these polymers on intracellular gene delivery is presented here with detailed analyses of cytotoxicity, cellular uptake efficiency, endocytosis pathway, subcellular distribution, and gene expression.