Endocytosis Mechanism of Nano Metal-Organic Frameworks for Drug Delivery

• Published in: Advanced healthcare materials 2016-09, Vol.5 (17), p.2261-2270
• Main Authors: Orellana-Tavra, Claudia, Mercado, Sergio A., Fairen-Jimenez, David
• Format: Article
• Language: English
• Subjects: Coated Materials, Biocompatible - chemistry; Coated Materials, Biocompatible - pharmacology; Degradation; drug delivery; Drug delivery systems; Drug Delivery Systems - methods; Endocytosis; Endocytosis - drug effects; Fluoresceins - chemistry; Fluoresceins - pharmacokinetics; Fluoresceins - pharmacology; HeLa Cells; Humans; Lysosomes; Lysosomes - metabolism; Markers; Metal-organic frameworks; nanoparticles; Nanoparticles - chemistry; Nanoparticles - therapeutic use; Organelles; Organometallic Compounds - chemistry; Organometallic Compounds - pharmacokinetics; Organometallic Compounds - pharmacology; Particle size; Uptakes
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.201600296

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@150UiO‐66 and cal@260UiO‐66, respectively), and shows that the active trafficking of cal@150UiO‐66 is done almost exclusively through clathrin‐mediated endocytosis, whereas the uptake of cal@260UiO‐66 is a combination of both clathrin and caveolae‐mediated endocytosis. Colocalization studies with a lysosomal marker showed that cal@150UiO‐66 is located mostly in lysosomes for further degradation, whereas cal@260UiO‐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. The study of the uptake mechanisms and final fate of a promising metal‐organic framework (MOF) is a crucial step for optimizing these materials for drug delivery applications. UiO‐66 particles of 260 nm are able to partially bypass the acidic degradation in the lysosomes whereas particles of 150 nm are destroyed in this compartment.