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Design and Fabrication of Dual Redox Responsive Nanoparticles with Diselenide Linkage Combined Photodynamically to Effectively Enhance Gene Expression

Authors Fang Y, Lin X, Jin X, Yang D, Gao S, Shi K, Yang M

Received 19 June 2020

Accepted for publication 24 August 2020

Published 1 October 2020 Volume 2020:15 Pages 7297—7314

DOI https://doi.org/10.2147/IJN.S266514

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 shikai@syphu.edu.cn; mingshi.yang@sund.ku.dk

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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