The fluorination effect on the transfection efficacy of cell penetrating peptide complexes
2022
Baoum, Abdulgader A.
Cell penetrating peptides (CPPs) have been used as alternative delivery vectors to translocate therapeutic cargo molecules across cell membranes. One example of CPPs is the dTAT peptide, which has shown great promise in the design of highly efficient and low-cytotoxic gene vectors when condensed via “soft” calcium cross links. Here, we investigated the effect of fluorination on the formulation of dTAT complexes and explored their potential for pDNA delivery to cells. Fluorinated dTAT complexes achieve excellent gene transfection efficacy compared to fluorinated PEI polyplexes in A549, HeLa, and MCF-7 cell lines. Furthermore, the fluorinated dTAT complexes exhibit excellent serum resistance, high gene transfection efficacy even in 10% FBS medium, and no detectable cytotoxicity on transfected cells. The optimum NaF concentration (14 mM) resulted in an over 1000-fold enhancement in dTAT complexes (N/P 33) transfection efficiency. According to these findings, fluorination seems to be a potential strategy for creating gene vectors without requiring complex syntheses.
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