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

Abstract

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/H 2 O 2 , dPSP4 degraded into small molecular weight cationic substances with low cytotoxicity rapidly. Singlet oxygen ( 1 O 2 ) 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.

Redox‐Responsive Polymeric Nanoparticle for Nucleic Acid Delivery and Cancer Therapy: Progress, Opportunities, and Challenges

“…Recently, the ROS/GSH dual‐responsive property of diselenide has been introduced in polymer nucleic acid vector for more efficient cancer therapy. Fang et al [ 401 ] reported a high molecular weight polymer dPSPs synthesized through crosslinking endogenous spermine by diselenide, which exhibited complete DNA compression, low cytotoxicity, and ideal proton buffering effect. Next, therapeutic pDNA and photosensitizer indocyanine green (ICG) were loaded in the synthesized polymeric vector to synthesize the polyplexes.…”