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• W2275578334 abstract "Cationic polymers have been turned into effective gene delivery agents by functionalizing with long-chain aliphatic lipids, but little information exists if small hydrophobic moieties can serve as effective substituents for this purpose. To explore this issue, we modified small molecular weight (1.2 kDa) polyethylenimine (1.2PEI) by a small hydrophobe, propionic acid (PrA), through N-acylation and investigated the efficacy of resultant polymers to deliver plasmid DNA (pDNA) to breast cancer cells MDA-231 and MCF-7. A significant impact of PrA grafting was observed on physicochemical features of polymers and resultant pDNA complexes. pDNA binding capacity, as measured by BC50 (weight ratio for 50% binding), was decreased from 0.25 to 0.64 with PrA substitution. Hydrodynamic size of polymer/pDNA complexes was not altered, but the surface charge (ξ-potential) was increased with low PrA substitution and decreased at higher PrA substitutions. Similarly, in vitro pDNA transfection efficacy in MDA-231 and MCF-7 cells was significantly increased with PrA grafting and optimum efficacy was observed in polymers with modest substitution, 0.25–1.0 PrAs/PEI (mol/mol), but higher substitutions was detrimental to transfection. The transfection efficiency of PEI-PrAs was higher than aliphatic lipid (linoleic acid) substituted PEI and more stable than 25 kDa branched PEI. However, unlike studies reported elsewhere, siRNA had no effect on transfection efficacy of pDNA/PEI-PrA complexes when used as an additive. We conclude that small hydrophobe substitution on low MW PEI converts it into effective pDNA delivery agent in breast cancer cells up to an optimal ratio, indicating that balancing hydrophobicity of polymer is critical for pDNA transfection. This manuscript investigated the influence of small hydrophobe (propionic acid, PrA, 3 carbon) grafted onto small molecular weight polyethylenimine (1.2PEI) in pDNA delivery. We have explored this approach as an alternative of common strategies to graft long chain and/or bulky lipids [linoleic acid (18 carbon), cholesterol]. At optimal substitution, transfection efficiency of these polymers was significantly higher than long chain lipid substituted 1.2PEI, emphasizing a proper hydrophobic/hydrophilic balance for optimum gene delivery. The overall results establish the feasibility of using small hydrophobes to create functional carriers, as long as the polymers are engineered with optimal ratio of substituent. The reported studies should facilitate the efforts of biomaterials scientists and engineers to design new carriers for gene therapy." @default.
• W2275578334 created "2016-06-24" @default.
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• W2275578334 date "2016-03-01" @default.
• W2275578334 modified "2023-10-15" @default.
• W2275578334 title "Small hydrophobe substitution on polyethylenimine for plasmid DNA delivery: Optimal substitution is critical for effective delivery" @default.
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• W2275578334 doi "https://doi.org/10.1016/j.actbio.2016.01.025" @default.
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