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Updated: Jun 27, 2026
Cell Labeling and Targeting with Superparamagnetic Iron Oxide Nanoparticles
Published on: October 19, 2015
Inhibition of tumor-cell invasion with chlorotoxin-bound superparamagnetic nanoparticles
Omid Veiseh1, Jonathan W Gunn, Forrest M Kievit
1Department of Materials Science and Engineering, University of Washington Seattle, WA 98195, USA.
Abstract:
Nanoparticles have been investigated as drug delivery vehicles, contrast agents, and multifunctional devices for patient care. Current nanoparticle-based therapeutic strategies for cancer treatment are mainly based on delivery of chemotherapeutic agents to induce apoptosis or DNA/siRNA to regulate oncogene expression. Here, 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, is presented. The nanoparticle comprises an iron oxide nanoparticle core conjugated with an amine-functionalized poly(ethylene glycol) silane and a small peptide, chlorotoxin (CTX), which enables the tumor cell-specific binding of the nanoparticle. It is shown that the nanoparticle exhibits substantially enhanced cellular uptake and an invasion inhibition rate of approximately 98% compared to unbound CTX ( approximately 45%). Significantly, the investigation from flow cytometry analysis, transmission electron microscopy, and fluorescent imaging reveals 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.
Insights
This study presents novel nanoparticles that inhibit cancer cell invasion and serve as imaging agents. These chlorotoxin-conjugated nanoparticles show high efficacy in blocking cancer cell invasion.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Nanoparticles are explored for cancer therapy, primarily via chemotherapy or gene regulation.
- Current strategies focus on apoptosis induction or oncogene expression modulation.
Purpose of the Study:
- To develop a nanoparticle system for cancer treatment by inhibiting cell invasion.
- To create a dual-function agent for both therapy and imaging (MRI/optical).
Main Methods:
- Conjugation of chlorotoxin (CTX) to iron oxide nanoparticles coated with PEGylated silane.
- Evaluation of cellular uptake and invasion inhibition rates.
- Analysis of MMP-2 activity and lipid raft internalization via flow cytometry, TEM, and fluorescence imaging.
Main Results:
- CTX-enabled nanoparticles achieved a ~98% invasion inhibition rate, significantly higher than unbound CTX (~45%).
- Nanoparticles deactivated membrane-bound matrix metalloproteinase 2 (MMP-2).
- Increased internalization of lipid rafts containing MMP-2 and ion channels was observed via receptor-mediated endocytosis.
Conclusions:
- The developed nanoparticle system offers a novel approach to cancer treatment by targeting cell invasion.
- Its dual diagnostic and therapeutic capabilities, coupled with MMP-2 inhibition, show potential for various cancer types.
- This platform could enable non-invasive diagnosis and treatment of cancers with upregulated MMP-2.
