Polyethylenimine-associated cerium oxide nanoparticles: A novel promising gene delivery vector

Abstract

Aims: The development of highly efficient and low toxic non-viral gene delivery vectors is the most challenging issues for successful application of gene therapy. A particular focus has been on understanding structure-activity relationships for transfection activity and toxicity of polyethylenimine (PEI). During the last decade, the use of cerium oxide nanoparticles (CeO₂-NPs) in biomedicine has attracted much attention due to their pH-dependent antioxidant activity. CeO₂-NPs provide protection normal cells from various forms of reactive oxygen species, but possess innate cytotoxicity and apoptosis to cancer cells. The purpose of this study was to design a new class of gene carriers by low molecular weight PEI (B-PEI 10 kDa) coordination onto CeO₂-NPs.

Main methods: B-PEI 10 kDa was conjugated to CeO₂-NPs by Epichlorohydrin linker. Transfection efficiency, cytotoxic and apoptotic effects of pDNA-PEI-CeO₂ NPs were evaluated on WEHI 164 cancer cells and normal L929 cells lines.

Key findings: PEI-CeO₂ NPs was able to condense the pDNA at carrier/plasmid (C/P) weight ratios of 0.5. The size and zeta potential of pDNA-PEI-CeO₂ NPs were 124 ± 7 nm and 22 ± 2 mV, respectively. The transfection efficacy of synthesized pDNA-PEI-CeO₂ NPs improved and the cytotoxicity was decreased compared to pDNA-PEI. Moreover, pDNA-PEI-CeO₂ NPs induced more apoptosis than unmodified PEI and CeO₂-NPs control groups. pDNA-PEI-CeO₂ NPs displayed more transfection, cytotoxicity, and apoptosis in WEHI 164 cancer cells than normal L929 cells.

Significance: In conclusion, PEI-CeO₂ nanocarriers could act as a potential candidate for gene and drug delivery to cancerous and tumor cells.

Keywords: Cerium oxide nanoparticles; Cytotoxicity; Gene delivery; Polyethylenimine; Transfection.