Department of Medical Biotechnology & Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Life Sci. 2019 Sep 1;232:116661. doi: 10.1016/j.lfs.2019.116661. Epub 2019 Jul 16.
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 (CeO-NPs) in biomedicine has attracted much attention due to their pH-dependent antioxidant activity. CeO-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 CeO-NPs.
B-PEI 10 kDa was conjugated to CeO-NPs by Epichlorohydrin linker. Transfection efficiency, cytotoxic and apoptotic effects of pDNA-PEI-CeO NPs were evaluated on WEHI 164 cancer cells and normal L929 cells lines.
PEI-CeO 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-CeO NPs were 124 ± 7 nm and 22 ± 2 mV, respectively. The transfection efficacy of synthesized pDNA-PEI-CeO NPs improved and the cytotoxicity was decreased compared to pDNA-PEI. Moreover, pDNA-PEI-CeO NPs induced more apoptosis than unmodified PEI and CeO-NPs control groups. pDNA-PEI-CeO NPs displayed more transfection, cytotoxicity, and apoptosis in WEHI 164 cancer cells than normal L929 cells.
In conclusion, PEI-CeO nanocarriers could act as a potential candidate for gene and drug delivery to cancerous and tumor cells.
开发高效低毒的非病毒基因传递载体是基因治疗成功应用的最具挑战性的问题。人们特别关注聚乙二烯亚胺(PEI)的转染活性和毒性的结构-活性关系。在过去的十年中,由于其 pH 依赖性抗氧化活性,氧化铈纳米粒子(CeO-NPs)在生物医学中的应用引起了广泛关注。CeO-NPs 为正常细胞提供了免受各种形式的活性氧的保护,但对癌细胞具有固有细胞毒性和细胞凋亡作用。本研究的目的是通过低分子量 PEI(B-PEI 10 kDa)与 CeO-NPs 的配位来设计一类新型基因载体。
通过表氯醇连接物将 B-PEI 10 kDa 连接到 CeO-NPs 上。在 WEHI 164 癌细胞和正常 L929 细胞系上评估 pDNA-PEI-CeO NPs 的转染效率、细胞毒性和凋亡作用。
PEI-CeO NPs 能够在载体/质粒(C/P)重量比为 0.5 时使 pDNA 凝聚。pDNA-PEI-CeO NPs 的大小和 zeta 电位分别为 124 ± 7nm 和 22 ± 2mV。与 pDNA-PEI 相比,合成的 pDNA-PEI-CeO NPs 的转染效率提高,细胞毒性降低。此外,pDNA-PEI-CeO NPs 诱导的凋亡比未修饰的 PEI 和 CeO-NPs 对照组更多。pDNA-PEI-CeO NPs 在 WEHI 164 癌细胞中的转染、细胞毒性和凋亡作用均高于正常 L929 细胞。
总之,PEI-CeO 纳米载体可以作为基因和药物传递到癌细胞和肿瘤细胞的潜在候选物。