Tumor growth requires lots of nutrients that are supplied through blood vessels. Angiogenesis, the process of growing new blood vessels, has been a target for destruction in cancer therapy with mixed results. The idea is simple: if one cannot fight a big army in the battlefield, perhaps something can be done on the army’s logistics of food and water.

Dr. David Cheresh of The Scripps Research Institute in La Jolla, California, a leading researcher in the field of angiogenesis, and his colleagues, in collaboration with a group from Stanford University led by Dr. Mark Bednarski, have designed nanoparticles to deliver weapons of mass destruction to cancer cells in mice, achieving dramatic results (Hood J.D. et al., Science 296:2404-2407, 2002).

Previously, Dr. Cheresh studied various kinds of blood vessels and found that an integrin, αvβ3, is expressed on newly growing blood vessels and rarely expressed on established old ones. The integrin, which is expressed on the surface of blood vessel-forming endothelial cells, has amenities of therapeutic potential: particles or viruses that are bound to it can be internalized and delivered into cells.

While αvβ3 integrin flags new blood vessels, a gene called Raf-1 plays a pivotal role in the molecular signaling cascade that leads to the formation of new blood vessels. They designed lipid-based nanoparticles whose surface was studded with ligands that can bind to αvβ3 and whose interior was loaded with a mutant form of the Raf-1 gene. Once inside the cells, some of the mutant Raf-1 gene will displace the normal ones and arrest the molecular process of forming new blood vessels.

When injected into tumor-bearing mice through the tail vein, the nanoparticles wiped out tumors of 400 mm³ in size, or the equivalent of a 2-kg tumor mass in an 80-kg person. Under the microscope, tumors die en masse around each blood vessel forming endothelial cell, indicative of mass apoptosis.

Transferring mouse research to humans has not been encouraging in the past. Dr. Cheresh’s attempt holds hope until proven otherwise.

(Discovery Medicine, Vol. 1, No. 11, p2, 2002)