Nanoparticles Enhance Scorpion Venom Anticancer Properties

Chlorotoxin affects brain cells through its interaction with a protein called MMP-2, which allows the penetration of normal and tumor cells through tissue barriers. Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMPs are secreted as inactive proproteins that are activated when cleaved by extracellular proteinases. Chlorotoxin exerts a dual effect on MMP-2: it inhibits the enzymatic activity of MMP-2 and causes a reduction in the surface expression of MMP-2.

Investigators at the University of Washington (Seattle, USA) attached chlorotoxin to nanoparticles comprising an iron oxide nanoparticle core conjugated with an amine-functionalized poly(ethylene glycol) silane. Nanoparticle bound and unbound chlorotoxin were administered to cultures of mouse brain cancer cells.

Results published in the January 19, 2009, issue of the journal Small revealed that the nanoparticles exhibited substantially enhanced cellular uptake and an invasion inhibition rate of nearly 98% as compared to the 45% invasion inhibition rate of the unbound chlorotoxin. Data from flow cytometry analysis, transmission electron microscopy, and fluorescent imaging showed that the chlorotoxin-enabled nanoparticles deactivated the cells' membrane-bound matrix MMP-2.
"People talk about the treatment being more effective with nanoparticles but they do not know how much, maybe 5% or 10%," said senior author Dr. Miqin Zhang, professor of materials science and engineering at the University of Washington. "This was quite a surprise to us."

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