Cholic acid modified 2 kDa polyethylenimine as efficient transfection agent

Abstract

New lipopolymers were synthesized by conjugating cholic acid (ChA) to polyethylenimines (PEI; 2 and 25 kDa) and a polyallylamine (PAA; 15 kDa) via N-acylation to develop effective gene delivery systems. The extent of ChA substitution linearly varied with the feed ratio during synthesis, indicating good control over grafting ratio. While ChA did not affect binding to plasmid DNA (pDNA) for higher molecular weight (MW) polymers, ChA substitution to 2 kDa PEI significantly affected the pDNA binding. Toxicity of the 2 kDa PEI was unaffected by ChA substitution, but it was improved for the higher MW polymers. Using immortal 293T cells and primary cord blood-derived mesenchymal stem cells, low MW (2 kDa) PEI was shown to display much better transfection efficiency as a result of ChA substitution, unlike the higher MW polymers. We conclude that ChA could be a suitable substituent for non-toxic (low MW) PEIs in order to improve their transfection efficiency.

Hydrophobe-substituted bPEI derivatives: boosting transfection on primary vascular cells

“…As expected from DNA complexation results, and as often reported for bPEI derivatives [29][30][31], the degree of substitution strongly influenced the transfection properties. Very high substitution degrees led to low efficiency (PEI2-St12, PEI2-LA9, PEI1.2-αLA6) both in PAoSMCs and HUASMCs.…”

Synergistic Inhibition of Human Carcinoma Cell Growth via Co-Delivery of p53 Plasmid DNA and bcl-2 Antisense Oligodeoxyribonucleotide by Cholic Acid-modified Polyethylenimine

“…Recently, conjugation of CA to PEI 25KDa has been reported to decrease cytotoxicity of PEI (5,18). Deoxycholic acid-modified PEI1.8KDa had lower cytotoxicity than PEI1.8KDa in human coronary artery smooth muscle cells (4).…”

Hydrophobically modified polyethylenimine-based ternary complexes for targeting brain tumor: stability, in vitro and in vivo studies

“…In case of hydrophobic modification, the anionic polymers can bind to the cationic PEI electrostatically to modify the complex surface. Such hydrophobic modification of low molecular weight PEI (2 kDa) using cholic acid resulting in its enhanced transfection efficiency has been previously reported (Dube et al 2013). During cellular uptake, aggregated PEI-pDNA complexes (having large size) are internalized with great difficulty but complexes with mean diameter less than 200 nm are easily internalized as the average diameter of endosomes is $100-200 nm (Murk et al 2003).…”