Amino Acid-Linked Low Molecular Weight Polyethylenimine for Improved Gene Delivery and Biocompatibility.
Xiao-Ru WuJi ZhangJu-Hui ZhangYa-Ping XiaoXi HeYan-Hong LiuXiao-Qi YuPublished in: Molecules (Basel, Switzerland) (2020)
The construction of efficient and low toxic non-viral gene delivery vectors is of great significance for gene therapy. Herein, two novel polycations were constructed via Michael addition from low molecular weight polyethylenimine (PEI) 600 Da and amino acid-containing linkages. Lysine and histidine were introduced for the purpose of improved DNA binding and pH buffering capacity, respectively. The ester bonds afforded the polymer biodegradability, which was confirmed by the gel permeation chromatography (GPC) measurement. The polymers could well condense DNA into nanoparticles and protect DNA from degradation by nuclease. Compared with PEI 25 kDa, these polymers showed higher transfection efficiency, lower toxicity, and better serum tolerance. Study of this mechanism revealed that the polyplexes enter the cells mainly through caveolae-mediated endocytosis pathway; this, together with their biodegradability, facilitates the internalization of polyplexes and the release of DNA. The results reveal that the amino acid-linked low molecular weight PEI polymers could serve as promising candidates for non-viral gene delivery.
Keyphrases
- amino acid
- dna binding
- gene therapy
- circulating tumor
- cell free
- single molecule
- sars cov
- induced apoptosis
- transcription factor
- mass spectrometry
- oxidative stress
- nucleic acid
- cell cycle arrest
- wastewater treatment
- tandem mass spectrometry
- gene expression
- signaling pathway
- high resolution
- endoplasmic reticulum stress
- heat shock protein
- ms ms
- dna methylation
- wound healing