Porous metal–organic-framework nanoscale carriers as a potential platform for drug delivery and imaging

Abstract

In the domain of health, one important challenge is the efficient delivery of drugs in the body using non-toxic nanocarriers. Most of the existing carrier materials show poor drug loading (usually less than 5 wt% of the transported drug versus the carrier material) and/or rapid release of the proportion of the drug that is simply adsorbed (or anchored) at the external surface of the nanocarrier. In this context, porous hybrid solids, with the ability to tune their structures and porosities for better drug interactions and high loadings, are well suited to serve as nanocarriers for delivery and imaging applications. Here we show that specific non-toxic porous iron(III)-based metal–organic frameworks with engineered cores and surfaces, as well as imaging properties, function as superior nanocarriers for efficient controlled delivery of challenging antitumoural and retroviral drugs (that is, busulfan, azidothymidine triphosphate, doxorubicin or cidofovir) against cancer and AIDS. In addition to their high loadings, they also potentially associate therapeutics and diagnostics, thus opening the way for theranostics, or personalized patient treatments.

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Figure 1
Figure 2
Figure 3: CDV (black), doxo (red) and AZT-TP (green) delivery under simulated physiological conditions (PBS, 37 C) from MIL-100 nanoparticles.
Figure 4: Magnetic resonance images.

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Acknowledgements

We acknowledge E. Legenre, M. Belle, F. Kani, C. Bellanger and E. Jubeli for their help with the experiments. We are grateful to J-M. Greneche, H. Chacun, M. Apple, C. Bories, H.Hillarieu, and O. David for their collaboration. We thank K. Storck, V. Huyot and R. Yousfi for their technical assistance with the AZT-TP experiments.

This work was partially supported by the CNRS, Université Paris Sud, Université de Versailles Saint-Quentin, EU funding through the ERC-2007-209241-BioMOFs, ERC and KOCI through the Institutional Research Program of KRICT. KRICT’s authors thank You-Kyong Seo for his experimental assistance.

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P.H., nanoMOF synthesis, surface modification of nanoparticles, drug and cosmetic encapsulation tests, toxicity assays, degradation tests,in vivo magnetic resonance imaging; C. Serre, nanoMOF synthesis, surface modification of nanoparticles, drug and cosmetic encapsulation tests, degradation tests, imaging applications; T.C., nanoMOF synthesis, PEG modification, drug encapsulation and delivery, in vitro toxicity assays, degradation tests, in vitro magnetic resonance imaging; B.G. and C. Sebrie, imaging applications; T.B., in vivo toxicity assays, nanoMOF degradation tests, doxorubicin encapsulation and delivery; J.F.E., nanoMOF degradation tests; D.H., synthesis of nanoparticles of MIL-101 _NH2; P. Clayette and C.K., anti-HIV activity of MIL-100 nanoparticles; J.-S.C. and Y.K.H., synthesis of nanoparticles of MIL-100 and MIL-53 in water; V.M., busulfan activity tests; P.-N.B. and L.C., liver function evaluation in the in vivo toxicity assays; S.G., activity of Cyp-450 in the in vivo toxicity assays; G.F., nanoMOF synthesis, surface modification of nanoparticles; P. Couvreur, drug encapsulation and delivery, toxicity assays, surface modification of nanoparticles; R.G., drug encapsulation and delivery, toxicity assays, surface modification of nanoparticles, imaging applications.

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Correspondence to Patricia Horcajada or Ruxandra Gref.

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Horcajada, P., Chalati, T., Serre, C. et al. Porous metal–organic-framework nanoscale carriers as a potential platform for drug delivery and imaging. Nature Mater 9, 172–178 (2010). https://doi.org/10.1038/nmat2608

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