Enhanced Transfection Efficiency of Low Generation PAMAM Dendrimer Conjugated with the Nuclear Localization Signal Peptide Derived from Herpesviridae.

Polyamidoamine (PAMAM) dendrimer is an extensively studied polymer in the biomedical research because of its low polydispersity, distinct molecular structure, and surface functionalities. Generally, a high-generational PAMAM dendrimer is used for gene delivery because transfection efficiency is dependent on charge density; however, an increase in charge density induces disruption of the cellular membrane, and damage to the membrane results in cytotoxicity. In this study, we selected PAMAM generation 2 to reduce the cytotoxic effect and conjugated RRILH and RRLHL sequences, nuclear localization signals (NLS) derived from herpesviridae to PAMAM generation 2. The transfection efficiency of RRILH-PAMAM G2 and RRLHL-PAMAM G2 was similar to that of polyethylenimine (PEI) in Neuro2A, HT22, and HaCaT cells, whereas their transfection efficiency was much higher than that of PEI in NIH3T3 cells. RRILH-PAMAM G2 showed relatively lower cytotoxicity than did RRLHL-PAMAM G2 in all cell lines, but the transfection capacity of the two polymers was similar. Our study shows that low-generational PAMAM dendrimer conjugated with NLS sequences has potential as an alternative to PEI in gene delivery.