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

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...

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Autores principales: Fang Y, Lin X, Jin X, Yang D, Gao S, Shi K, Yang M
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Publicado: Dove Medical Press 2020
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spelling oai:doaj.org-article:02731187211c4e4ba52a6e27c97f70092021-12-02T10:30:12ZDesign and Fabrication of Dual Redox Responsive Nanoparticles with Diselenide Linkage Combined Photodynamically to Effectively Enhance Gene Expression1178-2013https://doaj.org/article/02731187211c4e4ba52a6e27c97f70092020-10-01T00:00:00Zhttps://www.dovepress.com/design-and-fabrication-of-dual-redox-responsive-nanoparticles-with-dis-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yan 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, DenmarkCorrespondence: Kai Shi; Mingshi Yang Email shikai@syphu.edu.cn; mingshi.yang@sund.ku.dkBackground: 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 oxygenFang YLin XJin XYang DGao SShi KYang MDove Medical Pressarticlediselenidepolysperminebiodegradablegene deliverysingle-line oxygenMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 7297-7314 (2020)
institution DOAJ
collection DOAJ
language EN
topic diselenide
polyspermine
biodegradable
gene delivery
single-line oxygen
Medicine (General)
R5-920
spellingShingle diselenide
polyspermine
biodegradable
gene delivery
single-line oxygen
Medicine (General)
R5-920
Fang Y
Lin X
Jin X
Yang D
Gao S
Shi K
Yang M
Design and Fabrication of Dual Redox Responsive Nanoparticles with Diselenide Linkage Combined Photodynamically to Effectively Enhance Gene Expression
description 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, DenmarkCorrespondence: Kai Shi; Mingshi Yang Email shikai@syphu.edu.cn; mingshi.yang@sund.ku.dkBackground: 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
format article
author Fang Y
Lin X
Jin X
Yang D
Gao S
Shi K
Yang M
author_facet Fang Y
Lin X
Jin X
Yang D
Gao S
Shi K
Yang M
author_sort Fang Y
title Design and Fabrication of Dual Redox Responsive Nanoparticles with Diselenide Linkage Combined Photodynamically to Effectively Enhance Gene Expression
title_short Design and Fabrication of Dual Redox Responsive Nanoparticles with Diselenide Linkage Combined Photodynamically to Effectively Enhance Gene Expression
title_full Design and Fabrication of Dual Redox Responsive Nanoparticles with Diselenide Linkage Combined Photodynamically to Effectively Enhance Gene Expression
title_fullStr Design and Fabrication of Dual Redox Responsive Nanoparticles with Diselenide Linkage Combined Photodynamically to Effectively Enhance Gene Expression
title_full_unstemmed Design and Fabrication of Dual Redox Responsive Nanoparticles with Diselenide Linkage Combined Photodynamically to Effectively Enhance Gene Expression
title_sort design and fabrication of dual redox responsive nanoparticles with diselenide linkage combined photodynamically to effectively enhance gene expression
publisher Dove Medical Press
publishDate 2020
url https://doaj.org/article/02731187211c4e4ba52a6e27c97f7009
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AT jinx designandfabricationofdualredoxresponsivenanoparticleswithdiselenidelinkagecombinedphotodynamicallytoeffectivelyenhancegeneexpression
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AT gaos designandfabricationofdualredoxresponsivenanoparticleswithdiselenidelinkagecombinedphotodynamicallytoeffectivelyenhancegeneexpression
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AT yangm designandfabricationofdualredoxresponsivenanoparticleswithdiselenidelinkagecombinedphotodynamicallytoeffectivelyenhancegeneexpression
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