Abstract
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 ~9 KDa, they show good DNA binding ability. The formed polyplexes, which are stable toward serum but decomposed under ROS-conditions, have appropriate sizes (180~300 nm) and positive zeta-potentials (+35~50 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.
Highlights
Gene therapy is considered to be one of the most promising approaches to treating various human genetic and acquired diseases, such as cancers, aging, diabetes, and cardiovascular diseases [1].Safe and effective gene delivery vectors are a prerequisite for successful gene therapy [2,3]
The preparation route for the target polymers is shown in Scheme 2
The preparation the target polymers shown in Scheme22.inVarious aromaticof aldehydes aldehydes
Summary
Gene therapy is considered to be one of the most promising approaches to treating various human genetic and acquired diseases, such as cancers, aging, diabetes, and cardiovascular diseases [1].Safe and effective gene delivery vectors are a prerequisite for successful gene therapy [2,3]. Gene therapy is considered to be one of the most promising approaches to treating various human genetic and acquired diseases, such as cancers, aging, diabetes, and cardiovascular diseases [1]. Due to the high transfection efficiency (TE), viral carriers are a commonly used method of gene delivery. Their immunogenicity, toxicity, limited DNA packaging capacity, and difficulty in large-scale production have impeded their development and clinic applications [4,5]. In attempt to overcome these barriers, a broad range of versatile and efficient non-viral gene vectors have been developed. As one class of non-viral gene vectors, have acquired increasing attention due to their easy preparation and modification in recent years [6,7,8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
