Grall Romain, Hidalgo Tania, Delic Jozo, Garcia-Marquez Alfonso, Chevillard Sylvie, Horcajada Patricia
Laboratoire de Cancérologie Expérimentale, Service de Radiobiologie Expérimentale et Innovations Technologiques, Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Fontenay-aux-Roses, 8 Route du Panorama, 92265 Fontenay-aux-Roses, France.
J Mater Chem B. 2015 Nov 14;3(42):8279-8292. doi: 10.1039/c5tb01223f. Epub 2015 Sep 24.
The high porosity and versatile composition of the benchmarked mesoporous metal (Fe, Al, Cr) trimesate metal-organic frameworks (MIL-100(Fe, Al, Cr)) make them very promising solids in different strategic industrial and societal domains (separation, catalysis, biomedicine, etc.). In particular, MIL-100(Fe) nanoparticles (NPs) have been recently revealed to be one of the most promising and innovative next generation tools enabling multidrug delivery to overcome cancer resistance. Here, we analyzed the in vitro toxicity of the potential drug nanocarrier MIL-100(Fe) NPs and the effect of the constitutive cation by comparing its cytotoxicity with that one of its Cr and Al analogue NPs. Lung (A549 and Calu-3) and hepatic (HepG2 and Hep3B) cell lines were selected considering pulmonary, ingestion or intravenous exposure modes. First, the complete physicochemical characterization (structural, chemical and colloidal stability) of the MIL-100(Fe, Al, Cr) NPs was performed in the cell culture media. Then, their cytotoxicity was evaluated in the four selected cell lines using a combination of methods from cell impedance, cell survival/death and ROS generation to DNA damage for measuring genotoxicity. Thus, MIL-100(Fe, Al, Cr) NPs did not induce in vitro cell toxicity, even at high doses in the p53 wild type cell lines (A549 and calu-3 (lung) and HepG2 (liver)). The only toxic effect of MIL100-Fe was observed in the hepatocarcinoma cell line Hep3B, which is stress sensitive because it does not express TP53, the guardian of the genome.
基准介孔金属（铁、铝、铬）均苯三甲酸金属有机框架材料（MIL-100(Fe, Al, Cr)）具有高孔隙率和多功能组成，使其在不同的战略工业和社会领域（分离、催化、生物医学等）成为非常有前景的固体材料。特别是，最近发现MIL-100(Fe)纳米颗粒（NPs）是最有前景和创新性的下一代工具之一，能够实现多药递送以克服癌症耐药性。在此，我们通过将潜在药物纳米载体MIL-100(Fe) NPs与其铬和铝类似物纳米颗粒的细胞毒性进行比较，分析了其体外毒性以及组成阳离子的影响。考虑到肺部、摄入或静脉暴露模式，选择了肺（A549和Calu-3）和肝（HepG2和Hep3B）细胞系。首先，在细胞培养基中对MIL-100(Fe, Al, Cr) NPs进行了完整的物理化学表征（结构、化学和胶体稳定性）。然后，使用从细胞阻抗、细胞存活/死亡、活性氧生成到DNA损伤等一系列方法组合，在四种选定的细胞系中评估它们的细胞毒性，以测量遗传毒性。因此，即使在p53野生型细胞系（A549和Calu-3（肺）以及HepG2（肝））中高剂量使用时，MIL-100(Fe, Al, Cr) NPs也不会诱导体外细胞毒性。在肝癌细胞系Hep3B中观察到了MIL100-Fe的唯一毒性作用，该细胞系对压力敏感，因为它不表达基因组守护者TP53。
