CANCER RESEARCH
NANOPARTICLE GUIDED MISSILES
Tiny polymer beads are used to deliver deadly gene to tumor blood supply
Many cancer drugs currently in clinical trials act by inhibiting new blood vessel formation, or angiogenesis. Disruption of this process deprives tumors of the blood supply they need to grow. Now, scientists at Scripps Research Institute and Stanford Medical School have added a new weapon to the antiangiogenesis arsenal [Science, 296, 2404 (2002)].
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Cheresh
SCRIPPS BIOMEDICAL GRAPHICS PHOTO
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The team, led by Scripps immunologist David A. Cheresh, directs tiny polymer beads decorated with a small organic ligand specific for the integrin v3--a cell-surface molecule specific to endothelial cells of growing blood vessels--to the angiogenic blood vessels of tumor-bearing mice.
The cationic nanoparticles also carry a deadly weapon: DNA encoding a mutant form of Raf, a protein kinase common to all known angiogenic pathways. The angiogenic endothelial cells take up and express the mutant gene, which disrupts normal Raf function and blocks blood vessel growth.
When mice bearing a variety of different tumors were injected with the nanoparticles, their tumors shrank or disappeared with no apparent side effects.
No side effects are observed, Cheresh says, because "the nanoparticles selectively target the cells we wish to eliminate." And, unlike viral gene delivery methods, the protein-free polymer beads are unlikely to generate an immune response.
Scripps and Stanford have applied for patents on the technology, which Merck KGaA of Darmstadt, Germany, has licensed. But because many other antiangiogenic therapies that yielded remarkable results in mice have failed to meet expectations in the clinic, only time will tell whether the nanoparticles will find therapeutic use in humans.
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