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Cellular evaluation of the metal-organic framework PCN-224 associated with inflammation and autophagy
Toxicology in Vitro ( IF 2.6 ) Pub Date : 2020-10-12 , DOI: 10.1016/j.tiv.2020.105019
Xiuping Li 1 , Hua Qin 2 , Zehao Zhou 3 , Yang Li 2 , Ji Wang 2 , Mo Lin 1 , Xuemeng Dong 1 , Man Yang 2 , Lele Li 3
Affiliation  

Metal-organic frameworks (MOFs) are innovative porous structures consisting of metal ions and organic ligands, which have been verified for extraordinary applications in nanomedicine and pharmaceuticals. PCN-224 is a type of Zr-based MOFs, which has recently emerged as one of the most attractive nanomaterials for various applications, such as drug delivery, bioimaging and cancer therapy due to its favorable and fascinating physical-chemical properties. However, the safety evaluation and the potential toxicological properties remain unclear. In this study, the general cytotoxicity of PCN-224 were examined in both human hepatocytes L-02 cells and mouse macrophages RAW264.7. Furthermore, the effect of inflammation and autophagy were measured in L-02 cells. The results indicated that PCN-224 was engulfed in L-02 cells and subsequently resulted in morphological changes, cell membrane destruction, and oxidative stress in L-02 cells. PCN-224 might trigger inflammation by promoting the secretion of inflammatory factors such as Tumor necrosis factors (TNF-α) and Interleukin (IL-6). PCN-224 might induce autophagosome accumulation and subsequently autophagic dysfunction. Additionally, PCN-224 induced cytotoxicity in RAW264.7 cells and increased the protein levels of the inflammasome component NLR Family Pyrin Domain Containing 3 (NLRP3) molecular, which indicated its cellular effects in different cell types. All of these results will support the reasonable use of PCN-224.



中文翻译:

与炎症和自噬相关的金属有机骨架 PCN-224 的细胞评估

金属有机骨架 (MOF) 是一种创新的多孔结构,由金属离子和有机配体组成,已被证实在纳米医学和制药中具有非凡的应用。PCN-224 是一种基于 Zr 的 MOF,由于其有利和迷人的物理化学性质,它最近已成为各种应用中最具吸引力的纳米材料之一,例如药物递送、生物成像和癌症治疗。然而,安全性评估和潜在的毒理学特性仍不清楚。在这项研究中,PCN-224 的一般细胞毒性在人肝细胞 L-02 细胞和小鼠巨噬细胞 RAW264.7 中进行了检查。此外,在 L-02 细胞中测量了炎症和自噬的影响。结果表明,PCN-224被L-02细胞吞噬,随后导致L-02细胞发生形态变化、细胞膜破坏和氧化应激。PCN-224 可能通过促进炎症因子的分泌,如肿瘤坏死因子 (TNF-α) 和白细胞介素 (IL-6) 来引发炎症。PCN-224 可能会诱导自噬体积累和随后的自噬功能障碍。此外,PCN-224 在 RAW264.7 细胞中诱导细胞毒性并增加炎性体成分 NLR Family Pyrin Domain Containing 3 (NLRP3) 分子的蛋白质水平,这表明其在不同细胞类型中的细胞作用。所有这些结果都将支持 PCN-224 的合理使用。PCN-224 可能通过促进炎症因子的分泌,如肿瘤坏死因子 (TNF-α) 和白细胞介素 (IL-6) 来引发炎症。PCN-224 可能会诱导自噬体积累和随后的自噬功能障碍。此外,PCN-224 在 RAW264.7 细胞中诱导细胞毒性并增加炎性体成分 NLR Family Pyrin Domain Containing 3 (NLRP3) 分子的蛋白质水平,这表明其在不同细胞类型中的细胞作用。所有这些结果都将支持 PCN-224 的合理使用。PCN-224 可能通过促进炎症因子的分泌来引发炎症,例如肿瘤坏死因子 (TNF-α) 和白细胞介素 (IL-6)。PCN-224 可能会诱导自噬体积累和随后的自噬功能障碍。此外,PCN-224 在 RAW264.7 细胞中诱导细胞毒性并增加炎性体成分 NLR Family Pyrin Domain Containing 3 (NLRP3) 分子的蛋白质水平,这表明其在不同细胞类型中的细胞作用。所有这些结果都将支持 PCN-224 的合理使用。7 细胞并增加炎性体成分 NLR Family Pyrin Domain Containing 3 (NLRP3) 分子的蛋白质水平,表明其在不同细胞类型中的细胞作用。所有这些结果都将支持 PCN-224 的合理使用。7 细胞并增加炎性体成分 NLR Family Pyrin Domain Containing 3 (NLRP3) 分子的蛋白质水平,表明其在不同细胞类型中的细胞作用。所有这些结果都将支持 PCN-224 的合理使用。

更新日期:2020-10-30
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