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In vitro study demonstrates enhanced gene transfection and reduced cytotoxicity in HeLa cells using peptide-modified PAMAM dendrimers, indicating potential for targeted cancer gene therapy.
Because of the complex mechanisms mediating cancer onset, prognosis, and metastatic behavior, different therapeutic approaches targeting these mechanisms have been investigated. Recent advancements in nanocarrier-based drug and gene delivery methods have encouraged scientific groups to investigate various novel therapeutic techniques. In this study, a poly(amidoamine) (PAMAM) polymer-based gene carrier containing the cathepsin B-enzyme sensitive sequence (glycine-phenylalanine-leucine-glycine, GFLG) was evaluated to determine transfection efficiency. Following the GFLG sequence, the surface of PAMAM generation 4 (G4) was conjugated with histidine (H) and arginine (R) for improved endosomal escape and cellular uptake, respectively. The successful synthesis of G4-GLFG-H-R was confirmed by ¹H-nuclear magnetic resonance spectroscopy. The polyplex composed of G4-GLFG-H-R and pDNA was simulated by the enzyme cathepsin B and induced endosomal escape of pDNA, which was confirmed by gel electrophoresis. Compared with the G4 control, enzyme-sensitive G4-GLFG-H-R showed higher transfection efficiency and lower cytotoxicity in HeLa cells. These results demonstrated that G4-GLFG-H-R may be a highly potent and efficient carrier for gene therapy applications.
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Lee et al. (2017) studied this question.
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