Synthesis and Properties of Low-Molecular-Weight PEI-Based Lipopolymers for Delivery of DNA

Abstract

Rapid enzymatic degradation and fragmentation during DNA administration can result in limited gene expression, and consequently, poor efficacy. It is necessary to use novel vectors for DNA delivery. Herein, we aimed to design useful carriers for enhancing transfection efficiency (TE). These lipopolymers were prepared through Michael addition reactions from low-molecular-weight (LMW) polyethyleneimine (PEI) and linkers with three kinds of steroids. Agarose gel electrophoresis assay results displayed that the three lipopolymers could condense plasmid DNA well, and the formed polyplexes had appropriate sizes around 200–300 nm, and zeta potentials of about +25–40 mV. The results of in vitro experiments using HeLa, HEK293, and MCF-7 cells showed that these lipopolymers present higher TE than 25-kDa PEI, both in the absence and presence of 10% serum. Flow cytometry and confocal microscopy studies also demonstrated that these lipopolymer/DNA complexes present higher cellular uptake and intracellular distribution. The measurement of critical micelle concentration (CMC) revealed that these lipopolymers could form micelles, which are suited for drug delivery. All results suggest that the three materials may serve as hopeful candidates for gene and drug delivery in future in vivo applications.

Silencing of Gasdermin D by siRNA-Loaded PEI-Chol Lipopolymers Potently Relieves Acute Gouty Arthritis through Inhibiting Pyroptosis

“…Although PEI is a gold standard for nonviral gene transfection at present, the complex aggregation on the cell surface caused by strong cationic charge density results in severe cytotoxicity and the induction of necrosis. , Furthermore, many cholesterol (Chol)-based cationic lipids have been synthesized and utilized for gene delivery over the past decade because of the high safety and flexibility . In order to enhance transfection activities and decrease cytotoxicity, we designed highly hydrophobic cationic lipopolymers by grafting Chol onto PEI to enable specific siRNA therapy.…”

Alkylated Sulfonium Modification of Low Molecular Weight Polyethylenimine to Form Lipopolymers as Gene Vectors

“…Yang 28 This article is licensed under CC-BY-NC-ND 4 conjugated PEI with a phospholipid that contains two aliphatic chains on the glycerol skeleton. Other hydrophobic modifications such as folate 29 and cholesterol 30,31 have been investigated for the benefits of their targeting specificities. Sulfur-containing compounds have been widely studied for their vast application.…”

“…Yang conjugated PEI with a phospholipid that contains two aliphatic chains on the glycerol skeleton. Other hydrophobic modifications such as folate and cholesterol , have been investigated for the benefits of their targeting specificities.…”

Nanoparticle-Based Rifampicin Delivery System Development

“…The shell was composed of a positively charged polymer, polyethyleneimine (PEI), with three kinds of amine groups partially protonated at physiological and endosomal pH. Therefore, decoration of the nanoparticles with PEI shell enhances endosomal escape by its intrinsic “proton sponge effect” [ 21 ], and, simultaneously, demonstrates a wide array of electrostatic interactions with negatively dextran sulphate (DS) coating the core. DS, negatively charged polysaccharide, is a biodegradable and biocompatible polyanion which interacts electrostatically with the positive amino groups of CS and PEI [ 22 ].…”