Affiliation:
1. Key Laboratory of Functional Polymer Materials Ministry of Education Institute of Polymer Chemistry College of Chemistry Nankai University Tianjin 300071 China
2. Department of Biochemistry and Molecular Biology College of Life Science Nankai University Tianjin 300071 China
Abstract
AbstractA novel quinoline‐based thioketal‐containing zinc (II) coordinative module (Zn‐QS) is designed to transform common low‐molecular‐weight (LMW) polyethyleneimine (PEI) into a high‐performance siRNA carrier (Zn‐PQ) with self‐fluorescence and reactive oxygen species (ROS)‐responsiveness. In the multifunctional module, a quinoline derivative, frequently serving as pharmacophore, is utilized as the highly biocompatible ligand, and the Zn (II) coordinative quinoline‐based ligand also provides the robust self‐fluorescence character. And the ROS‐responsive thioketal spacer is introduced to trigger the siRNA controlled release into cytoplasm. Consequently, by the synergistic effects between Zn‐QS and LMW PEI on improving several crucial transfection‐efficiency‐related steps, the representative Zn‐PQ4 exhibits very high transfection efficiency of 1.8 and 2.5‐folds commercial Lipo2k and PEI25k in stem cell rADSC, respectively, >90% of transfection rates in a variety of conventional cell lines (3T3, HK‐2, HepG2, 293T, HeLa, PANC‐1), and 98.4% and 99.9% EGFP knockdown rates in 293T and HepG2 cells, respectively. Furthermore, Zn‐PQ4/siRNA polyplexes can circumvent various obstacles existing in systemic application to accumulate in heart, liver, and kidney and greatly silence the DNA expression in vivo. This work demonstrates the promising application prospects of the resulting efficient siRNA carriers in siRNA‐mediated gene therapy and fluorescence‐guided research.
Funder
National Natural Science Foundation of China
Fundamental Research Funds for the Central Universities
Subject
Electrochemistry,Condensed Matter Physics,Biomaterials,Electronic, Optical and Magnetic Materials
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献