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dc.contributor.authorTeplensky, Michelleen
dc.contributor.authorFantham, Marcusen
dc.contributor.authorLi, Pen
dc.contributor.authorWang, TCen
dc.contributor.authorMehta, Joshuaen
dc.contributor.authorYoung, Laurenceen
dc.contributor.authorMoghadam, Pen
dc.contributor.authorHupp, JTen
dc.contributor.authorFarha, OKen
dc.contributor.authorKaminski, Clemensen
dc.contributor.authorFairen Jimenez, Daviden
dc.date.accessioned2017-08-14T14:49:16Z
dc.date.available2017-08-14T14:49:16Z
dc.date.issued2017-06-07en
dc.identifier.issn0002-7863
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/266360
dc.description.abstractUtilizing 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.
dc.description.sponsorshipM.H.T. thanks the Gates Cambridge Trust for funding, S. Haddad, D. Vulpe and Dr. C. Hockings for helpful discussions, and Dr. J. McMillan at the Cambridge Advanced Imaging Centre (CAIC), University of Cambridge. D.F.-J. thanks the Royal Society for funding through a University Research Fellowship. O.K.F. and J.T.H. gratefully acknowledge DTRA for financial support (grant HDTRA-1-14-1-0014). C.F.K. acknowledges funding from the UK Engineering and Physical Sciences Research Council, EPSRC (grants EP/L015889/1 and EP/H018301/1), the Wellcome Trust (grants 3-3249/Z/16/Z and 089703/Z/09/Z) and the UK Medical Research Council, MRC (grants MR/K015850/1 and MR/K02292X/1), and Infinitus (China) Ltd. Computational work was supported by the Cambridge High Performance Computing Cluster, Darwin.
dc.languageengen
dc.language.isoenen
dc.publisherAmerican Chemical Society
dc.titleTemperature Treatment of Highly Porous Zirconium-Containing Metal-Organic Frameworks Extends Drug Delivery Release.en
dc.typeArticle
prism.endingPage7532
prism.issueIdentifier22en
prism.publicationDate2017en
prism.publicationNameJournal of the American Chemical Societyen
prism.startingPage7522
prism.volume139en
dc.identifier.doi10.17863/CAM.12601
dcterms.dateAccepted2017-05-16en
rioxxterms.versionofrecord10.1021/jacs.7b01451en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2017-06-07en
dc.contributor.orcidFantham, Marcus [0000-0002-9921-3334]
dc.contributor.orcidMehta, Joshua [0000-0002-9824-3697]
dc.contributor.orcidKaminski, Clemens [0000-0002-5194-0962]
dc.contributor.orcidFairen Jimenez, David [0000-0002-5013-1194]
dc.identifier.eissn1520-5126
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBBSRC (BB/H023917/1)
pubs.funder-project-idEPSRC (EP/H018301/1)
pubs.funder-project-idMRC (MR/K02292X/1)
pubs.funder-project-idMRC (G0902243)
pubs.funder-project-idWellcome Trust (089703/Z/09/Z)
pubs.funder-project-idMRC (MR/K015850/1)
pubs.funder-project-idEPSRC (EP/L015889/1)
cam.issuedOnline2017-05-16en
rioxxterms.freetoread.startdate2018-05-16


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