Development of Novel Tumor-Targeted Theranostic Nanoparticles Activated by Membrane-Type Matrix Metalloproteinases for Combined Cancer Magnetic Resonance Imaging and Therapy
dc.contributor.author | Ansari, C. | * |
dc.contributor.author | Tikhomirov, G.A. | * |
dc.contributor.author | Hong, S.H. | * |
dc.contributor.author | Falconer, Robert A. | * |
dc.contributor.author | Loadman, Paul | * |
dc.contributor.author | Gill, Jason H. | * |
dc.contributor.author | Castaneda, R. | * |
dc.contributor.author | Hazard, F.K. | * |
dc.contributor.author | Tong, L. | * |
dc.contributor.author | Lenkov, O.D. | * |
dc.contributor.author | Felsher, D.W. | * |
dc.contributor.author | Rao, J. | * |
dc.contributor.author | Daldrup-Link, H.E. | * |
dc.date.accessioned | 2016-08-17T14:48:52Z | |
dc.date.available | 2016-08-17T14:48:52Z | |
dc.date.issued | 2014-02-04 | |
dc.identifier.citation | Ansari 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. | |
dc.identifier.uri | http://hdl.handle.net/10454/8822 | |
dc.description | No | |
dc.description.abstract | A 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. | |
dc.description.sponsorship | Yorkshire Cancer Research | |
dc.language.iso | en | |
dc.subject | Nanoparticles | |
dc.subject | Iron oxide | |
dc.subject | Cancer therapy | |
dc.subject | MR imaging | |
dc.subject | Theranostic | |
dc.subject | MMP-14 | |
dc.subject | REF 2014 | |
dc.title | Development of Novel Tumor-Targeted Theranostic Nanoparticles Activated by Membrane-Type Matrix Metalloproteinases for Combined Cancer Magnetic Resonance Imaging and Therapy | |
dc.status.refereed | Yes | |
dc.type | Article | |
dc.type.version | No full-text in the repository | |
dc.identifier.doi | https://doi.org/10.1002/smll.201301456 | |
dc.openaccess.status | closedAccess | |
dc.date.accepted | 2013-08-27 |