Abstract
The development of gene delivery vectors with high efficiency and biocompatibility is one of the key points of gene therapy. A series of polycations were prepared from polyethylenimine (PEI) with several amino acids or their analogs. The target polymers have different charge and hydrophilic/hydrophobic properties, which may affect their performance in the gene transfection process. Gel retardation and DLS assays showed that these polymers may condense DNA into nanoparticles with positive zeta potentials and proper sizes for cellular uptake. Luciferase reporter gene transfection results revealed their higher transfection efficiency than PEI; especially in the presence of serum, in which up to 23 times higher efficiency was achieved by employing glycolic acid-grafted PEI. Moreover, it was found that the degree of substitution on PEI has an apparent influence on the transfection, and the balance between electron-positive/negative groups largely affects the delivery process. The higher serum tolerance was also proven by BSA adsorption, flow cytometry and confocal microscopy assays. Results demonstrate that such type of polycations may serve as promising non-viral gene delivery vectors.
Highlights
As an important type of non-viral gene delivery vectors, cationic polymers have received attention for their good stability, easy preparation, and modification [1,2]
The results indicate that the transfection mediated by these polymers was more effective than that obtained in the experiment involving PEI
Branched PEI (25 kDa) was modified with several amino acids or other functional acids to give the derivative polymers with various degrees of substitution (DS)
Summary
As an important type of non-viral gene delivery vectors, cationic polymers have received attention for their good stability, easy preparation, and modification [1,2]. The leading polymeric materials for gene delivery include polyethylenimine (PEI) [3,4], poly(L-lysine) [5], poly(tertiaryamine methacrylate) [3], and polyamidoamine [6], etc Among these polymers, PEI was most widely studied due to its easy availability. High molecular weight (HMW) PEI, especially that with the Mw of 25 kDa, has relatively higher tranfection efficiency (TE) both in vitro and in vivo. This made it the golden standard for the design of novel polymeric vectors [7,8,9]. To develop novel PEI-based materials with both high TE and improved biocompatibility is of great importance
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