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

Int J Nanomedicine. 2020 Oct 1:15:7297-7314. doi: 10.2147/IJN.S266514. eCollection 2020.

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/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: biodegradable; diselenide; gene delivery; polyspermine; single-line oxygen.

MeSH terms

  • Animals
  • Cross-Linking Reagents / chemistry
  • Gene Expression / drug effects*
  • Gene Transfer Techniques*
  • Glutathione / chemistry
  • Hemolysis / drug effects
  • Hydrogen Peroxide / chemistry
  • Indocyanine Green / chemistry
  • Infrared Rays
  • Mice
  • Molecular Weight
  • NIH 3T3 Cells
  • Nanoparticles / chemistry*
  • Nanoparticles / therapeutic use
  • Oxidation-Reduction
  • Particle Size
  • Phototherapy / methods
  • Plasmids
  • Polymers / chemical synthesis
  • Polymers / chemistry*
  • Singlet Oxygen / chemistry
  • Spectroscopy, Fourier Transform Infrared
  • Spermine / chemistry
  • Transfection

Substances

  • Cross-Linking Reagents
  • Polymers
  • Singlet Oxygen
  • Spermine
  • Hydrogen Peroxide
  • Glutathione
  • Indocyanine Green

Grants and funding

The authors wish to thank the National Natural Science Foundation of China (No. 31671020, 81971729) for financial support. The authors declare no competing financial interest.