Yan Fang,1 Xiaojie Lin,2 Xuechao Jin,2 Dongjuan Yang,2 Shan Gao,2 Kai Shi,2 Mingshi Yang1,3 1Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, People’s Republic of China; 2Department of Pharmaceutics, School of Pharmaceutical Science, Shenyang Pharmaceutical University, Shenyang 117004, People’s Republic of China; 3Department of Pharmacy, Faculty of Health and Medical Sciences, University of model planes Copenhagen, Copenhagen O DK-2100, DenmarkCorrespondence: Kai Shi; Mingshi Yang Email [email protected]; mingshi.yang@sund.
ku.dkBackground: PEI is currently the most used non-viral gene copyright and the transfection efficiency is closely related to the molecular weight; however, the prominent problem is that the cytotoxicity increased with the molecular weight.Methods: A novel redox responsive biodegradable diselenide cross-linked polymer (dPSP) was designed to enhance gene expression.ICG-pEGFP-TRAIL/dPSP nanoparticles with high drug loading are prepared, which have redox sensitivity and plasmid protection.
The transfection efficiency of dPSP nanoparticle was evaluated in vitro.Results: The plasmid was compressed by 100% at the N/P ratio of 16, and the particle size was less than 100 nm.When explored onto high concentrations of GSH/H2O2, dPSP4 degraded into small molecular weight cationic substances with low cytotoxicity rapidly.Singlet oxygen (1O2) was produced when indocyanine green (ICG) was irradiated by near-infrared laser irradiation (NIR) to promote oxidative degradation of dPSP4 nanoparticles.
Under the stimulation of NIR 808 and redox agent, the particle size and PDI of ICG-pDNA/dPSP nanoparticle increased significantly.Conclusion: Compared with gene therapy alone, co-transportation of dPSP4 nanoparticle with ICG and pEGFP-TRAIL had better antitumor effect.Diselenide-crosslinked polyspermine had a promising prospect on gene delivery and preparation of Smoker multifunctional anti-tumor copyright.Keywords: diselenide, polyspermine, biodegradable, gene delivery, single-line oxygen.