Department of Chemical Engineering and Biotechnology, University of Cambridge, CB2 3RA, Cambridge, UK.
Adv Healthc Mater. 2016 Sep;5(17):2261-70. doi: 10.1002/adhm.201600296. Epub 2016 Jul 6.
The pathway of internalization and final fate of a specific metal-organic framework (MOF) in cells has been investigated for the first time. This study is based on two calcein-loaded UiO-66 samples with particle sizes of 150 and 260 nm (i.e., cal@150 UiO-66 and cal@260 UiO-66, respectively), and shows that the active trafficking of cal@150 UiO-66 is done almost exclusively through clathrin-mediated endocytosis, whereas the uptake of cal@260 UiO-66 is a combination of both clathrin and caveolae-mediated endocytosis. Colocalization studies with a lysosomal marker showed that cal@150 UiO-66 is located mostly in lysosomes for further degradation, whereas cal@260 UiO-66 seems to avoid the lysosomal degradation and potentially deliver the cargo molecules in the cytosol, allowing their distribution to different cellular organelles. This study reveals the importance of the internalization processes of MOFs, particularly the relevance of their particle size, and also the critical significance of their final fate to become an efficient drug delivery system. Based on these results, it is possible that extremely small particle-sized MOFs are not the most efficient carriers and instead relatively medium-sized particles are required.
首次研究了特定金属有机骨架（MOF）在细胞内内化途径和最终归宿。这项研究基于两种粒径分别为 150nm 和 260nm 的载钙黄绿素 UiO-66 纳米颗粒（即 cal@150 UiO-66 和 cal@260 UiO-66），结果表明 cal@150 UiO-66 的主动转运几乎完全通过网格蛋白介导的内吞作用进行，而 cal@260 UiO-66 的摄取则是网格蛋白和小窝蛋白介导的内吞作用的组合。与溶酶体标记物的共定位研究表明，cal@150 UiO-66 主要位于溶酶体中进行进一步降解，而 cal@260 UiO-66 似乎避免了溶酶体降解，并可能将货物分子递送至细胞质中，从而允许其分布到不同的细胞细胞器。这项研究揭示了 MOFs 内化过程的重要性，特别是其粒径的相关性，以及其最终归宿对成为有效药物传递系统的关键意义。基于这些结果，可能是粒径极小的 MOFs 并不是最有效的载体，而相对中等大小的颗粒则是必需的。
