N-Butyltriphenylphosphonium Bromide-linear PEI Polymers Mediated Efficient Gene Transfection

Gene therapy has inspired various researchers due to its potential of treating inherited disorders; however, many problems remain to be resolved such as development of a safe and efficient vector to overcome major hurdles of the gene transfer at the cellular level. To address these issues, various modifications have been incorporated in cationic polymers. Among these, hydrophobic modifications have also been considered; however, such modifications affect the solubility of the polymers post modification. In an attempt overcome this concern, we have deliberately selected a hydrophobic ligand bearing a charged moiety, i.e. Butyltriphenylphosphonium bromide (TPP⁺). A series of triphenylphosphonium bromide-grafted-linear polyethylenimine (BTP) polymers have been synthesized and characterized by physicochemical techniques prior to their evaluation for transfection efficacy and cytotoxicity. Subsequently, the BTP polymers were assessed for their buffering capacity, intracellular trafficking and transfection studies in mammalian cell lines and found to exhibit significantly higher transfection efficiency compared to the standard transfection reagents. The versatility of the projected vector was established by sequential delivery of GFP-specific siRNA, which resulted in efficient knockdown of the targeted gene expression. The study demonstrates that the BTP polymers can serve as efficient vectors for the delivery of nucleic acids in future gene therapy applications.