Liver Cancer Cell Targeting Gene Delivery Using Lactobionic Acid-Functionalized Dendrimers as Non-viral Vectors

摘要

Development of highly efficient non-viral gene delivery vectors for targeting delivery to cancer cells still remains a great challenge.In this study,we report a new gene delivery vector based on lactobionic acid-functionalized amine-terminated generation 5 poly(amidoamine) dendrimers (G5.NH2-La),which is able to effectively target human liver cancer cells (e.g.HepG2 cells).La moieties were successfully modified on the surface of dendrimers,which was confirmed by 1H NMR spectroscopy.The compaction of pDNA encoding luciferase (Luc) using both G5.NH2-La and G5.NH2 dendrimers was compared by agarose gel retardation assay.The gene transfection efficiency was evaluated by Luc assay.It shows that the G5.NH2-La dendrimers are able to compact the pDNA effectively at the lower N/P ratios,similar to the unmodified G5.NH2 dendrimers.The transfection efficiency of G5.NH2-La dendrimers was 3.2 times higher than that of G5.NH2 dendrimers at the N/P ratio of 2.5 ∶ 1.The significantly improved gene transfection efficiency of G5.NH2-La dendrimers is primarily due to the ability of lactobionic acid-mediated targeting of HepG2 cells.G5.NH2-La dendrimers may have the potential to be used as a new gene delivery vector for targeted gene therapy of liver cancer cells.