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PEGylation of polypropylenimine dendrimers : effects on cytotoxicity, DNA condensation, gene delivery and expression in cancer cells

Somani, Sukrut and Laskar, Partha and Altwaijry, Najla and Kewcharoenvong, Paphitchaya and Irving, Craig and Robb, Gillian and Pickard, Benjamin S. and Dufès, Christine (2018) PEGylation of polypropylenimine dendrimers : effects on cytotoxicity, DNA condensation, gene delivery and expression in cancer cells. Scientific Reports, 8. ISSN 2045-2322

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    Abstract

    Diaminobutyric polypropylenimine (DAB) dendrimers have been shown to be highly efficient non-viral gene delivery systems for cancer therapy. However, their cytotoxicity currently limits their applications. To overcome this issue, PEGylation of DAB dendrimer, using various PEG molecular weights and dendrimer generations, has been attempted to decrease the cytotoxicity and enhance the DNA condensation, size and zeta potential, cellular uptake and transfection efficacy of these dendriplexes. Among all the PEGylated dendrimers synthesized, generation 3- and generation 4-DAB conjugated to low molecular weight PEG (2 kDa) at a dendrimer: DNA ratio of 20:1 and 10:1 resulted in an increase in gene expression on almost all tested cancer cells lines (by up to 3.2-fold compared to unmodified dendrimer in A431 cells). The highest level of β-galactosidase gene expression (10.07x10E-3 ± 0.09x10E-3 U/mL) was obtained following treatment of B16F10-Luc cells with G4-dendrimer PEGylated with PEG2K at a dendrimer: DNA ratio of 20:1. These delivery systems significantly decreased cytotoxicity on B16F10-Luc cells, by more than 3.4-fold compared to unmodified dendrimer. PEGylated generations 3- and 4-DAB dendrimers are therefore promising gene delivery systems for cancer therapy, combining low cytotoxicity and high transfection efficacy.