no / 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. / Yorkshire Cancer Research
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/8822 |
| Date | 27 August 2013 |
| Creators | Ansari, C., Tikhomirov, G.A., Hong, S.H., Falconer, Robert A., Loadman, Paul, Gill, Jason H., Castaneda, R., Hazard, F.K., Tong, L., Lenkov, O.D., Felsher, D.W., Rao, J., Daldrup-Link, H.E. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, published version paper |
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