Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 9, Issue 41, Pages 35516-35525Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.7b07342
Keywords
metal-organic frameworks; metabolic pathways; drug delivery; endocytosis
Funding
- Becas Chile
- Cambridge Trust
- Royal Society
- University of Glasgow
- EPSRC [EP/L004461/1]
- EU ERC [Co 615954]
- Spanish MINECO [SEV-2013-0295]
- ERC-COG [726380]
- [2014-SGR-80]
- [MAT2015-65354-C2-1-R]
- EPSRC [EP/L004461/1] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [EP/L004461/1] Funding Source: researchfish
- European Research Council (ERC) [726380] Funding Source: European Research Council (ERC)
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A critical bottleneck for the use of metal-organic frameworks (MOFs) as drug delivery systems has been allowing them to reach their intracellular targets without being degraded in the acidic environment of the lysosomes. Cells take up particles by endocytosis through multiple biochemical pathways, and the fate of these particles depends on these routes of entry. Here, we show the effect of functional group incorporation into a series of Zr-based MOFs on their endocytosis mechanisms, allowing us to design an efficient drug delivery system. In particular, naphthalene-2,6-dicarboxylic acid and 4,4 ' biphenyldicarboxylic acid ligands promote entry through the caveolin-pathway, allowing the particles to avoid lysosomal degradation and be delivered into the cytosol and enhancing their therapeutic activity when loaded with drugs.
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