Surface-Engineered Dendrimers with a Diaminododecane Core Achieve Efficient Gene Transfection and Low Cytotoxicity
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Abstract
Cationic dendrimers are widely used as gene vectors; however, these materials are usually associated with unsatisfied transfection efficiency and biocompatibility. In this study, we used an aliphatic hydrocarbon-cored polyamidoamine (PAMAM) dendrimer as an alternative to traditional cationic PAMAM dendrimers in the design of efficient gene vectors. Diaminododecane-cored generation 4 (C12G4) PAMAM dendrimer showed dramatically higher efficacy in luciferase and EGFP gene transfection than diaminoethane-cored generation 4 (C2G4) and diaminohexane-cored generation 4 (C6G4) PAMAM dendrimers. The viability of cells incubated with C12G4 at transfection concentrations is above 90%. The significantly improved gene transfection efficacy of C12G4 is attributed to the hydrophobic core of C12G4 which increases the cellular uptake of dendrimer/DNA polyplexes. Further modification of C12G4 with functional ligands such as arginine, 2,4-diamino-1,3,5-triazine, and fluorine compounds significantly increase its transfection efficiency on several cell lines. These results suggest that diaminododecane-cored dendrimers can be developed as a versatile scaffold in the design of efficient gene vectors.
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