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纳米沸石咪唑酯骨架 8(ZIF-8)暴露于人类胚胎肾(HEK293)和结肠癌细胞(SW480)系中的细胞毒性、氧化应激和细胞凋亡。

Cytotoxicity, oxidative stress, and apoptosis in human embryonic kidney (HEK293) and colon cancer (SW480) cell lines exposed to nanoscale zeolitic imidazolate framework 8 (ZIF-8).

机构信息

Department of Fisheries, Faculty of Natural Resources, University of Kurdistan, P.O. Box 416, Sanandaj, 66177-15175, Iran.

Department of Zrebar Lake Environmental Research, Kurdistan Studies Institute, University of Kurdistan, Sanandaj, Iran.

出版信息

Environ Sci Pollut Res Int. 2021 Oct;28(40):56772-56781. doi: 10.1007/s11356-021-14636-5. Epub 2021 Jun 1.

DOI:10.1007/s11356-021-14636-5
PMID:34060017
Abstract

Zinc (zeolitic) imidazolate framework 8 (ZIF-8) has been widely considered in the literature as an ideal candidate for drug delivery especially anti-cancer drugs. However, the available information on the biocompatibility and cytotoxicity of ZIF-8 nanoparticles is contradictory. Therefore, in the present study, the ZIF-8 particles were synthetized, characterized, and their potential toxicity on two eukaryotic cell lines including human embryonic kidney (HEK293) and human colon cancer (SW480) cells was investigated in vitro. The characterization of ZIF-8 particles by TEM, EDX, SEM, and DLS indicated the synthesis of the hexagonal crystals with mean diameter of 124.71±32.74 nm and the presence of the zinc element at 86.25% by weight (wt%) of the ZIF-8 structure. The results of the cytotoxicity assessment of ZIF-8 NPs showed that the viability of two different cell lines reduced significantly coincident with increasing exposure concentration from 0 to 500 μg mL (P<0.05). The 24-h half-inhibitory concentration (IC50-24 h) values of ZIF-8 NPs for HEK293 and SW480 cell lines were 116.22 and 36.23 μg mL, respectively. We found that the viability of SW480 cells was significantly lower than the HEK293 cells in all exposure concentrations of ZIF-8 NPs except control. Exposure of both cells resulted in increasing of the intracellular reactive oxygen species (ROS) production and activation of apoptosis pathway. The apoptosis rate of cancer SW480 cells was higher than the normal HEK293 cells. These findings indicate that synthetized ZIF-8 NPs could be a candidate for cancer therapy, although their toxic effects on the normal cells also should be considered.

摘要

锌(沸石咪唑酯骨架)8(ZIF-8)在文献中被广泛认为是药物输送的理想候选物,特别是抗癌药物。然而,关于 ZIF-8 纳米粒子的生物相容性和细胞毒性的可用信息是相互矛盾的。因此,在本研究中,合成、表征了 ZIF-8 颗粒,并在体外研究了它们对两种真核细胞系(包括人胚肾(HEK293)和人结肠癌细胞(SW480))的潜在毒性。TEM、EDX、SEM 和 DLS 对 ZIF-8 颗粒的表征表明,合成了具有 124.71±32.74nm 平均直径的六方晶体,并且锌元素在 ZIF-8 结构中的重量百分比(wt%)为 86.25%。ZIF-8 NPs 细胞毒性评估的结果表明,两种不同细胞系的活力随着暴露浓度从 0 增加到 500μg mL(P<0.05)而显著降低。ZIF-8 NPs 对 HEK293 和 SW480 细胞系的 24 小时半抑制浓度(IC50-24 h)值分别为 116.22 和 36.23μg mL。我们发现,除对照外,在 ZIF-8 NPs 的所有暴露浓度下,SW480 细胞的活力均明显低于 HEK293 细胞。两种细胞的暴露均导致细胞内活性氧(ROS)产生增加和凋亡途径激活。SW480 癌细胞的凋亡率高于正常 HEK293 细胞。这些发现表明,合成的 ZIF-8 NPs 可能是癌症治疗的候选物,尽管它们对正常细胞的毒性作用也应考虑在内。

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