Journal
MOLECULES
Volume 23, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/molecules23082061
Keywords
reactive oxygen species (ROS); stimuli responsive; gene delivery; cationic polymer; non-viral vectors
Funding
- National Science Foundation of China [2170021243]
- Science and Technology Department of Sichuan Province [2015JY0115]
- Fundamental Research Funds for the Central Universities, Southwest Minzu University [2018HQZZ19]
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In this report, a series of polycations are designed and synthesized by conjugating reactive oxygen species (ROS)-responsive thioacetal-linkers to low molecular weight (LMW) polyethylenimine (PEI) via ring-opening polymerization. Their structure-activity relationships (SARs) as gene delivery vectors are systematically studied. Although the MWs of the target polymers are only similar to 9 KDa, they show good DNA binding ability. The formed polyplexes, which are stable toward serum but decomposed under ROS-conditions, have appropriate sizes (180 similar to 300 nm) and positive zeta-potentials (+35 similar to 50 mV). In vitro experiments reveal that these materials have low cytotoxicity, and higher transfection efficiency (TE) than controls. Furthermore, the title polymers exhibit excellent serum tolerance. With the present of 10% serum, the TE of the polymers even increases up to 10 times higher than 25 KDa PEI and 9 times higher than Lipofectamine 2000. The SAR studies also reveal that electron-withdrawing groups on the aromatic ring in 4a may benefit to balance between the DNA condensation and release for efficient gene transfection.
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