Synthesis and Gene Transfection Efficacies of PEI−Cholesterol-Based Lipopolymers

Abstract

Nine lipopolymers based on low molecular weight polyethyleneimines (PEI) and cholesterol via an ether linkage between the polymer amine and the cholesterol backbone have been synthesized. Different percentage of cholesterol moieties have been grafted on three types of PEI of molecular weights 800, 1200, and 2000. These lipopolymers were studied for gene transfection activities in HeLa cells. All the lipopolymers were first optimized for enhanced transfection efficacies as coliposomes with DOPE. All lipopolymers are better transfecting agents and highly serum compatible than commercially available PEI-25KDa. Transfection efficacies and serum compatibility of lipopolymers were found to be dependent upon the MW of PEI used for lipopolymer synthesis and percentage of cholesterol grafting on lipopolymers. Cell viability assay showed that PEI-25KDa is highly toxic as compared to all the lipopolymers. Lipopolyplexes were characterized by transmission electron microscopy, which showed the presence of spherical aggregates.

A self-assembled polymeric micellar immunomodulator for cancer treatment based on cationic amphiphilic polymers

“…S1) and the FT-IR (Fig. S2) spectra of SPI exhibited a unique peak denoting an amide bond between PEI and ATRA, confirming the conjugation of these molecules (Table S1) [25]. The particle size of SPI was 67 ± 1 nm, while its surface charge was 40 ± 1 mV.…”

A Potential Targeting Gene Vector Based on Biotinylated Polyethyleneimine/Avidin Bioconjugates

“…The in vitro cytotoxicities of ABP and ABP/pDNA complexes were examined by MTT assay following literature procedures (36). 25 kDa PEI and PEI/pDNA complexes were used as the control.…”

Stability and toxicity of empty or gene-loaded lipopolysaccharide-amine nanopolymersomes

“…5,9,10 Alternatively, cholesterol modification has been proved to be an effective strategy to increase both the stability and the gene transfection efficacy of polyplexes, which may be realized by alleviating serum inhibition, enhancing the cellular/nuclear uptake, and decreasing cytotoxicity. 4,5,7,[11][12][13][14][15][16][17] Additionally, introducing anionic polymer such as anionic polysaccharide is able to improve the polyplex stability and the transfection efficiency by conferring the charge shielding and biodegradability, aiding the rupture of endo-/lysosome and gene release and decreasing cytotoxicity. 5,[18][19][20][21][22] Based on these studies, we engineered a novel brush copolymer of lipopolysaccharide-amine (LPSA) as a cytosolic delivery vector by introducing anionic polysaccharide of oxidized alginate (OA) and Cho to polyethyleneimine (PEI) with molecular weight of 1.8k dalton (PEI 1.8k), where OA and Cho-graft-PEI act as the backbone and side chains, respectively.…”