期刊
ADVANCED HEALTHCARE MATERIALS
卷 5, 期 17, 页码 2261-2270出版社
WILEY-BLACKWELL
DOI: 10.1002/adhm.201600296
关键词
drug delivery; endocytosis; metal-organic frameworks; nanoparticles
资金
- Becas Chile
- Cambridge Trust
- Royal Society (UK)
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.
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