Sugar-Coating The Problem
Even with such potent drugs in the pipeline, another problem must be overcome before anti-cancer drugs will work well. Some solid tumors are so large that it is difficult to get any anti-cancer drug to penetrate deeply inside the tumor. David Ranney says that chemotherapy works initially to shrink the outside of these tumors. But the inside never gets the drug and becomes resistant to it by the start of the next chemotherapy regimen.

At home, patients endure a roller coaster of hope and despair as their regressing tumors regrow. Ranney estimates that 95 percent of standard chemotherapy agents are cleared from the body's bloodstream before ever making contact with a tumor cell. That's because the body is so good at ridding itself of toxic drugs via the liver. "No delivery, no payload," says Ranney, who founded two biotech companies and now runs a Dallas consulting company called Global Biomedical Solutions.

For enough of a drug to reach the core of a large, solid tumor, many patients must withstand massive doses of toxic chemotherapy that kill bone marrow and sometimes heart cells. Raphael Pollock, chair of the department of surgical oncology and head of the division of surgery at the MD Anderson Cancer Center, relays the story of three such unlucky patients. All were cured of tumors in their muscles and other soft tissues, but the chemotherapy's side effects required each to undergo a heart transplant.

"Obviously the treatments we have are less than ideal," says Pollock. But Ranney, attempting to improve drug targeting and action, has turned to a clever means of encapsulation. As a pathologist at Northwestern University and elsewhere, Ranney observed that white blood cells and viruses were two of the biological agents that could penetrate deep into tissue cells. He also noted that the cells and germs performed their fait accompli by covering themselves in sugar. Why not cloak anti-cancer drugs in the same biological coats that nature has devised?

The concept led Ranney and his colleagues at the University of Texas Southwestern Medical Center to manufacture a platform of sugar-based coverings called sulfated glycosaminoglycans. Various types of sugars are mixed with anti-colon cancer drugs, emulsified under high pressure, and freeze dried. The powder is later dissolved and injected into various strains of mice, each with differing solid tumors. Once inside the animal's bloodstream, the sugars recognize special molecular receptors on the inner surfaces of blood vessel walls, similar to locating a house by its address. The sugars then bind to those sites, pulling the drug with them through the vessel wall and into the nearby tissue. There, the sugar disguises the drug from the body's clearance mechanism and eventually leads the drugs into the depths of the tumor--to their final "street address," Ranney says. "We are fooling the body into transporting our own drugs for targeting."

As a bonus, Ranney's team encapsulates the drugs in a time-release package that releases the chemotherapy payload slowly and over a longer time, ensuring that a tumor does not shrink slightly only to regrow soon after remission.

So far, Ranney's work is in its early stages. In one strain of tested mice, 40 percent experienced complete regression of their tumors after 90 days with the sugar-coated drug, compared with 0 percent in control animals given non-experimental forms of drugs. "With current advances in chemistry," Ranney sums up, "we are now moving from exposed, highly toxic drugs to packages of payloads that get the home address of the tumor cell."

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