PAMAM Dendrimer Conjugated with Cell-penetrating Peptide-derived Oligopeptides for Enhanced Cell Uptake and Gene Delivery

Cell‐penetrating peptides (CPPs), originated from membrane translocating sequences of viruses, can deliver biomolecules effectively into cells. Research on natural and synthetic CPPs, for delivering drugs and genes reveals that this process requires cellular uptake independent of receptors and endosomes to minimize damage to the cell membrane. To this end, we conjugated CPP‐derived oligopeptides to the surface of polyamidoamine (PAMAM) dendrimers to develop novel nanocarriers that improve cellular uptake transfection efficiency. PAMAM generation 4 (G4) was conjugated with oligopeptides composed of lysine and phenylalanine (KFF, FFK). The DNA condensation efficiency of PAMAM G4‐KFF and PAMAM G4‐FFK was determined using an agarose gel retardation assay. The sizes of the polyplexes were determined using dynamic light scattering as well as scanning and transmission electron microscopy. Cytotoxicity and transfection efficiency were evaluated using the HeLa and HepG2 cells. The transfection efficiencies of PAMAM G4‐KFF and PAMAM G4‐FFK were comparable with that of the gold‐standard transfection reagent polyethylenimine (PEI25 kDa). These results suggest that these nanocarriers will serve as efficient non‐viral vehicles for gene therapy.