Laboratory for Particles-Biology Interactions, Department of Materials Meet Life, Swiss Federal Laboratories for Materials Science and Technology (Empa), Lerchenfeldstrasse 5, 9014 St. Gallen, Switzerland.
Nanoparticle Systems Engineering Laboratory, Institute of Process Engineering, Department of Mechanical and Process Engineering, ETH Zurich, Sonneggstrasse 3, 8092 Zurich, Switzerland.
ACS Appl Mater Interfaces. 2023 Aug 16;15(32):38367-38380. doi: 10.1021/acsami.3c08818. Epub 2023 Aug 7.
Metal-organic frameworks (MOFs) have found increasing applications in the biomedical field due to their unique properties and high modularity. Although the limited stability of MOFs in biological environments is increasingly recognized, analytical techniques have not yet been harnessed to their full potential to assess the biological fate of MOFs. Here, we investigate the environment-dependent biochemical transformations of widely researched nanosized MOFs (nMOFs) under conditions relevant to their medical application. We assess the chemical stability of antimicrobial zinc-based drug delivery nMOFs (Zn-ZIF-8 and Zn-ZIF-8:Ce) and radio-enhancer candidate nMOFs (Hf-DBA, Ti-MIL-125, and TiZr-PCN-415) containing biologically nonessential group IV metal ions. We reveal that even a moderate decrease in pH to values encountered in lysosomes (pH 4.5-5) leads to significant dissolution of ZIF-8 and partial dissolution of Ti-MIL-125, whereas no substantial dissolution was observed for TiZr-PCN-415 and Hf-DBA nMOFs. Exposure to phosphate-rich buffers led to phosphate incorporation in all nMOFs, resulting in amorphization and morphological changes. Interestingly, long-term cell culture studies revealed that nMOF (bio)transformations of, e.g., Ti-MIL-125 were cellular compartment-dependent and that the phosphate content in the nMOF varied significantly between nMOFs localized in lysosomes and those in the cytoplasm. These results illustrate the delicate nature and environment-dependent properties of nMOFs across all stages of their life cycle, including storage, formulation, and application, and the need for in-depth analyses of biotransformations for an improved understanding of structure-function relationships. The findings encourage the considerate choice of suspension buffers for MOFs because these media may lead to significant material alterations prior to application.
金属-有机骨架（MOFs）由于其独特的性质和高的模块性，在生物医学领域的应用越来越广泛。尽管 MOFs 在生物环境中的稳定性有限已经得到越来越多的认识，但分析技术尚未被充分利用来评估 MOFs 的生物命运。在这里，我们研究了在与医学应用相关的条件下，广泛研究的纳米级 MOFs（nMOFs）的环境依赖性生化转化。我们评估了含生物非必需四价金属离子的抗菌锌基药物输送 nMOFs（Zn-ZIF-8 和 Zn-ZIF-8:Ce）和放射增强候选 nMOFs（Hf-DBA、Ti-MIL-125 和 TiZr-PCN-415）的化学稳定性。我们揭示了即使 pH 值适度下降到溶酶体中遇到的 pH 值（4.5-5），也会导致 ZIF-8 显著溶解和 Ti-MIL-125 的部分溶解，而 TiZr-PCN-415 和 Hf-DBA nMOFs 则没有明显的溶解。暴露于富含磷酸盐的缓冲液中会导致所有 nMOFs 中都掺入磷酸盐，导致非晶化和形态变化。有趣的是，长期细胞培养研究表明，nMOF（生物）转化，例如 Ti-MIL-125，取决于细胞区室，并且 nMOF 中的磷酸盐含量在溶酶体中和细胞质中的 nMOF 之间差异显著。这些结果说明了 nMOFs 在其整个生命周期的所有阶段（包括储存、配方和应用）的脆弱性和环境依赖性性质，以及需要深入分析生物转化以更好地了解结构-功能关系。这些发现鼓励对 MOFs 的悬浮缓冲液进行谨慎选择，因为这些介质在应用之前可能会导致显著的材料改变。
