Department of Chemical and Biomedical Engineering, Benjamin M. Statler College of Engineering and Mineral Resources, West Virginia University, Morgantown, WV 26506, USA.
Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown WV 26506, USA.
Int J Nanomedicine. 2019 Sep 17;14:7583-7591. doi: 10.2147/IJN.S215950. eCollection 2019.
The flexibility and tunability of metal organic frameworks (MOFs), crystalline porous materials composed of a network of metal ions coordinated by organic ligands, confer their variety of applications as drug delivery systems or as sensing and imaging agents. However, such properties also add to the difficulty in ensuring their safe implementation when interaction with biological systems is considered.
In the current study, we used real-time sensorial strategies and cellular-based approaches to allow for fast and effective screening of two MOFs of prevalent use, namely, MIL-160 representative of a hydrophilic and ZIF-8 representative of a hydrophobic framework. The two MOFs were synthesized "in house" and exposed to human bronchial epithelial (BEAS-2B) cells, a pertinent toxicological screening model.
Analysis allowed evaluation and differentiation of particle-induced cellular effects as well identification of different degrees and routes of toxicity, all in a high-throughput manner. Our results show the importance of performing screening toxicity assessments before introducing MOFs to biomedical applications.
Our proposed screening assays could be extended to a wider variety of cell lines to allow for identification of any deleterious effects of MOFs, with the range of toxic mechanisms to be differentiated based on cell viability, morphology and cell-substrate interactions, respectively.
Our analysis highlights the importance of considering the physicochemical properties of MOFs when recommending a MOF-based therapeutic option or MOFs implementation in biomedical applications.
金属有机骨架（MOFs）是由金属离子与有机配体配位形成的网络结构的结晶多孔材料，具有灵活性和可调节性，因此在药物输送系统或传感和成像剂等方面有广泛的应用。然而，当考虑与生物系统相互作用时，这些特性也增加了确保其安全实施的难度。
在本研究中，我们使用实时传感策略和基于细胞的方法，快速有效地筛选两种常用的 MOF，即代表亲水性的 MIL-160 和代表疏水性骨架的 ZIF-8。这两种 MOF 是在“内部”合成的，并暴露于人类支气管上皮（BEAS-2B）细胞，这是一种相关的毒理学筛选模型。
分析允许评估和区分颗粒诱导的细胞效应，并确定不同程度和毒性途径，所有这些都是在高通量的方式下进行的。我们的结果表明，在将 MOF 引入生物医学应用之前，进行筛选毒性评估非常重要。
我们提出的筛选测定方法可以扩展到更广泛的细胞系，以识别 MOF 的任何有害影响，并根据细胞活力、形态和细胞-基底相互作用，分别区分不同的毒性机制。
我们的分析强调了在推荐基于 MOF 的治疗选择或在生物医学应用中实施 MOF 时，考虑 MOF 的物理化学性质的重要性。
