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Molecules 2018, 23(8), 2061; https://doi.org/10.3390/molecules23082061

Aromatic Thioacetal-Bridged ROS-Responsive Nanoparticles as Novel Gene Delivery Vehicles

College of Chemistry and Environmental Protection Engineering, Southwest Minzu University, Chengdu 610041, China
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Received: 16 July 2018 / Revised: 10 August 2018 / Accepted: 11 August 2018 / Published: 17 August 2018
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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. View Full-Text
Keywords: reactive oxygen species (ROS); stimuli responsive; gene delivery; cationic polymer; non-viral vectors reactive oxygen species (ROS); stimuli responsive; gene delivery; cationic polymer; non-viral vectors
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Lin, G.-Q.; Yi, W.-J.; Liu, Q.; Yang, X.-J.; Zhao, Z.-G. Aromatic Thioacetal-Bridged ROS-Responsive Nanoparticles as Novel Gene Delivery Vehicles. Molecules 2018, 23, 2061.

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