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Temperature Treatment of Highly Porous Zirconium-Containing Metal–Organic Frameworks Extends Drug Delivery Release

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    Temperature Treatment of Highly Porous Zirconium-Containing Metal–Organic Frameworks Extends Drug Delivery Release
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    † Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, U.K.
    ‡ Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States
    § Department of Chemistry, University of Cambridge, Cambridge, U.K.
    ∥ Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
    *[email protected]
    *[email protected]
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    Cite this: J. Am. Chem. Soc. 2017, 139, 22, 7522–7532
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    https://doi.org/10.1021/jacs.7b01451
    Published May 16, 2017
    Copyright © 2017 American Chemical Society
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    Abstract

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    Utilizing metal–organic frameworks (MOFs) as a biological carrier can lower the amount of the active pharmaceutical ingredient (API) required in cancer treatments to provide a more efficacious therapy. In this work, we have developed a temperature treatment process for delaying the release of a model drug compound from the pores of NU-1000 and NU-901, while taking care to utilize these MOFs’ large pore volume and size to achieve exceptional model drug loading percentages over 35 wt %. Video-rate super-resolution microscopy reveals movement of MOF particles when located outside of the cell boundary, and their subsequent immobilization when taken up by the cell. Through the use of optical sectioning structured illumination microscopy (SIM), we have captured high-resolution 3D images showing MOF uptake by HeLa cells over a 24 h period. We found that addition of a model drug compound into the MOF and the subsequent temperature treatment process does not affect the rate of MOF uptake by the cell. Endocytosis analysis revealed that MOFs are internalized by active transport and that inhibiting the caveolae-mediated pathway significantly reduced cellular uptake of MOFs. Encapsulation of an anticancer therapeutic, alpha-cyano-4-hydroxycinnamic acid (α-CHC), and subsequent temperature treatment produced loadings of up to 81 wt % and demonstrated efficacy at killing cells beyond the burst release effect.

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    Supporting Information

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/jacs.7b01451.

    • Structure of NU-1000 and NU-901, N2 adsorption isotherms at 77 K, and thermogravimetry curves under N2 atmosphere (PDF)

    • Reconstruction of a 3D image using the optical sectioning capabilities of SIM showing a HeLa cell with NU-1000 located within its boundaries (MOV)

    • Comparison of the dynamics of MOFs in both inter- and extracellular space with this 2-color 60-s time lapse video showing the movement of NU-1000 in 8× real time (MOV)

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