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dc.contributor.authorAnsari, C.*
dc.contributor.authorTikhomirov, G.A.*
dc.contributor.authorHong, S.H.*
dc.contributor.authorFalconer, Robert A.*
dc.contributor.authorLoadman, Paul*
dc.contributor.authorGill, Jason H.*
dc.contributor.authorCastaneda, R.*
dc.contributor.authorHazard, F.K.*
dc.contributor.authorTong, L.*
dc.contributor.authorLenkov, O.D.*
dc.contributor.authorFelsher, D.W.*
dc.contributor.authorRao, J.*
dc.contributor.authorDaldrup-Link, H.E.*
dc.date.accessioned2016-08-17T14:48:52Z
dc.date.available2016-08-17T14:48:52Z
dc.date.issued2014-02-04
dc.identifier.citationAnsari C,,Tikhomirov GA, Hong SH, Falconer RA, Loadman PM, Gill JH, Castaneda R, Hazard FK, Tong L, Lenkov OD, Felsher DW, Rao J and Daldrup-Link HE (2014) Development of Novel Tumor-Targeted Theranostic Nanoparticles Activated by Membrane-Type Matrix Metalloproteinases for Combined Cancer Magnetic Resonance Imaging and Therapy. Small, 10 (3): 566–575.en_US
dc.identifier.urihttp://hdl.handle.net/10454/8822
dc.descriptionnoen_US
dc.description.abstractA major drawback with current cancer therapy is the prevalence of unrequired doselimiting toxicity to non-cancerous tissues and organs, which is further compounded by a limited ability to rapidly and easily monitor drug delivery, pharmacodynamics and therapeutic response. In this report, the design and characterization of novel multifunctional “theranostic” nanoparticles (TNPs) is described for enzyme-specifi c drug activation at tumor sites and simultaneous in vivo magnetic resonance imaging (MRI) of drug delivery. TNPs are synthesized by conjugation of FDA-approved iron oxide nanoparticles ferumoxytol to an MMP-activatable peptide conjugate of azademethylcolchicine (ICT), creating CLIOICTs (TNPs). Signifi cant cell death is observed in TNP-treated MMP-14 positive MMTVPyMT breast cancer cells in vitro, but not MMP-14 negative fi broblasts or cells treated with ferumoxytol alone. Intravenous administration of TNPs to MMTV-PyMT tumor-bearing mice and subsequent MRI demonstrates signifi cant tumor selective accumulation of the TNP, an observation confi rmed by histopathology. Treatment with CLIO-ICTs induces a significant antitumor effect and tumor necrosis, a response not observed with ferumoxytol. Furthermore, no toxicity or cell death is observed in normal tissues following treatment with CLIO-ICTs, ICT, or ferumoxytol. These fi ndings demonstrate proof of concept for a new nanotemplate that integrates tumor specifi city, drug delivery and in vivo imaging into a single TNP entity through attachment of enzyme-activated prodrugs onto magnetic nanoparticles. This novel approach holds the potential to signifi cantly improve targeted cancer therapies, and ultimately enable personalized therapy regimens.en_US
dc.description.sponsorshipYorkshire Cancer Researchen_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttp://onlinelibrary.wiley.com/doi/10.1002/smll.201301456/fullen_US
dc.subjectNanoparticles; Iron oxide; Cancer therapy; MR imaging; Theranostic; MMP-14; REF 2014en_US
dc.titleDevelopment of Novel Tumor-Targeted Theranostic Nanoparticles Activated by Membrane-Type Matrix Metalloproteinases for Combined Cancer Magnetic Resonance Imaging and Therapyen_US
dc.status.refereedYesen_US
dc.date.Accepted2013-08-27
dc.typeArticleen_US
dc.type.versionpublished version paperen_US


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