Inhibition of tumor-cell invasion with chlorotoxin-bound superparamagnetic nanoparticles.
Inhibition of tumor-cell invasion with chlorotoxin-bound superparamagnetic nanoparticles.
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DOI：
10.1002/smll.200800646
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发表时间：
2009-02
期刊：
影响因子：
13.3
通讯作者：
Zhang, Miqin
中科院分区：
文献类型：
--
作者：
Veiseh, Omid;Gunn, Jonathan W.;Kievit, Forrest M.;Sun, Conroy;Fang, Chen;Lee, Jerry S. H.;Zhang, Miqin
Nanoparticles have been investigated as drug delivery vehicles, contrast agents, and multifunctional devices for patient care. Current nanoparticle-based therapeutic strategies for cancer treatment have been mainly based on delivery of chemotherapeutic agents to induce apoptosis or DNA/siRNA to regulate oncogene expression. Here, we present a nanoparticle system that demonstrates an alternative approach to the treatment of cancers, through the inhibition of cell invasion, while serving as a magnetic resonance and optical imaging contrast agent. The nanoparticle is comprised of an iron oxide nanoparticle core, conjugated with an amine-functionalized PEG silane and a small peptide, chlorotoxin (CTX), which enables the tumor cell-specific binding of the nanoparticle. We show that the nanoparticle exhibits substantially enhanced cellular uptake and an invasion inhibition rate of ~98% compared to unbound CTX (~45%). Significantly, our investigation from flow cytometry analysis, transmission electron microscopy and fluorescent imaging revealed that the CTX-enabled nanoparticles deactivated the membrane-bound matrix metalloproteinase 2 (MMP-2) and induced increased internalization of lipid rafts that contain surface-expressed MMP-2 and volume-regulating ion channels through receptor-mediated endocytosis, leading to enhanced prohibitory effects. Since upregulation and activity of MMP-2 have been observed in tumors of neuroectodermal origin, and in cancers of the breast, colon, skin, lung, prostate, ovaries and a host of others, this nanoparticle system can be potentially used for non-invasive diagnosis and treatment of a variety of cancer types.
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