The drugs cancer patients take to destroy their tumors also cause debilitating side effects such as nausea, weight loss, and even heart problems. But now researchers report that they can curb the spread of cancer cells in mice with drug concentrations far lower than the standard dose. The key is using a microscopic particle that zeroes in on blood vessels around the tumor to deliver low doses of the drug in a more concentrated way.
Metastasis--the ability to spread that makes cancer so pernicious--requires that the primary tumor is well-fed by an ever-expanding network of blood vessels. Without a constant supply of nutrients and oxygen, the tumor stays put. This blood-vessel expansion, called angiogenesis, takes place in certain healthy tissues as well. One thing that distinguishes tumor angiogenesis is a cell receptor called avß3, which is found on the inner wall of the blood vessels that feed the tumor.
A team led by University of California, San Diego, pathologist David Cheresh decided to target this receptor with a tiny particle, or nanoparticle, made up of fat-related compounds. To test the strategy, the researchers added very low doses of an anticancer drug called doxorubicin (Dox) to the particles and injected them into mice implanted with human pancreatic tumor cells. Dox disrupts DNA replication, and the scientists hoped to limit the drug's impact to the tumor vessels. After 11 days, mice that received the targeted nanoparticle infused with Dox showed about 82% less metastasis to a nearby lymph node than did mice that received Dox-carrying nanoparticles that didn't attach to the avß3 receptors. The primary tumor also shrank slightly in the mice that received the avß3-targeted Dox nanoparticles.
In traditional chemotherapy regimens, Dox is simply injected into a patient's bloodstream. Cheresh and his team found that this method had no impact on metastasis in the mice. To achieve the desired effect without nanoparticles, the researchers had to increase the concentration of Dox by 15-fold--a level that caused the mice to lose about 18% of their body weight. Mice injected with the lower dose on targeted nanoparticles lost only about 0.8% of body weight, the team reports online this week in the Proceedings of the National Academy of Sciences.
Cheresh says the study adds further weight to the idea that nanoparticles can enable scientists to achieve the same antitumor effects with a lower drug dosage. "It would be a very dramatic improvement in the way drugs are given," he says.
Gregory Lanza, a nanomedicine specialist at Washington University in St. Louis, Missouri, was pleased though not surprised by the results, calling them "another brick on the pile" of evidence supporting targeted therapies. Lanza, who was not affiliated with the study but has conducted similar work, says scientists will need a better understanding of tumor angiogenesis to know where in the system or at what point in the tumor's development they should administer the therapy to get the best results.