Utilization of Glycosaminoglycans/Proteoglycans as Carriers for Targeted Therapy Delivery

Figure 5

Schematic illustration of cellular uptake of plasmid DNA/Tf-PEG-PEI (nanoparticles) polyplexes, their shielding from nonspecific interaction, and the mechanism of action of shRNA (adapted from [43]). Internalization of PEG-shielded and Tf-R-targeted polyplexes into target cells occurs by receptor-mediated endocytosis after association of polyplex ligand Tf to Tf-R present on the target cell plasma membrane. Internalized particles are trafficked to endosomes followed by endosomal release of the particles and/or the nucleic acid into cytoplasm. Released siRNA will form a RNA-induced silencing complex and will be guided for cleavage of complementary target mRNA in the cytoplasm. siRNA (antisense) guide strand will direct the targeted RNAs to be cleaved by RNA endonuclease. Finally plasmid/Tf-PEG-PEI-nanoparticles delivery in the target cell shows reporter gene expression and activity.