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 10kDa) coordination onto CeO2-NPs. Main methods: B-PEI 10kDa 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 ± 7nm and 22 ± 2mV, respectively. The transfection efficacy of synthesized pDNA-PEI-CeO2 NPs improved and the cytotoxicity was decreased compared to pDNAPEI. 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.

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