Design and Fabrication of Dual Redox Responsive Nanoparticles with Diselenide Linkage Combined Photodynamically to Effectively Enhance Gene Expression
Received 19 June 2020
Accepted for publication 24 August 2020
Published 1 October 2020 Volume 2020:15 Pages 7297—7314
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Linlin Sun
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 Copenhagen, Copenhagen O DK-2100, Denmark
Correspondence: Kai Shi; Mingshi Yang Email firstname.lastname@example.org; email@example.com
Background: PEI is currently the most used non-viral gene carrier 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 multifunctional anti-tumor carrier.
Keywords: diselenide, polyspermine, biodegradable, gene delivery, single-line oxygen
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