An increased density of hyaluronic acid receptors is a characteristic of numerous cancers, and researchers combined the sugar with the drug to enhance specificity for malignant cells. They added the large copolymer to increase retention of the drug within cancer cells. When the investigators tested the bioconjugate form of the drug, they found it effective against breast, ovarian, and colon cancer cells grown in tissue culture.

"It's a new way of targeting anticancer drugs to cells," said Jindrich Kopecek, a co-author.

Glenn D. Prestwich, lead author of the new study, said that although some other methods of targeting chemotherapy at cancer cells also show promise, "you need to have an arsenal of weapons, not just a single weapon" to fight cancer.

In their study, Prestwich, Kopecek, and colleagues tested various combinations of doxorubicin with a polymer and hyaluronic acid.

There are elevated levels of hyaluronic acid receptors on cells for many tumors, including breast, ovarian, colon, and stomach cancers and leukemic cells, and the density of receptors appears to increase the likelihood of metastasis. When tumor cells bind to the hyaluronic acid attached to the doxorubicin molecule, the drug is released "in the tumor cell but not anywhere else," Prestwich said.

In the second part of the current study, doxorubicin was combined with a substance called HPMA copolymer, a small molecule attached to a large polymer. The combination is being tested in human trials in Europe, Kopecek said. The combination allows cancer patients to be treated with doxorubicin even if they have developed resistance to it because the copolymer prevents the cancer cells from pumping the doxorubicin out of the cell.

Because the combination of copolymer and doxorubicin is not selectively delivered to tumor cells, researchers added the third ingredient -- hyaluronic acid -- to serve as a targeting mechanism.

The triple combination of doxorubicin, HPMA copolymer, and hyaluronic acid was tested on cultured breast cancer cells and was 10 times more effective in killing them than when just doxorubicin-copolymer was used. Recent results show the triple combination is 50 times more effective in killing prostate cancer cells, although that finding is not part of the article, Prestwich added.

When the triple combination was administered to noncancerous mouse skin cells in culture, it was not toxic to them.

Although animal and human studies will be needed to prove the value of the new approach, the newly published study "is a nice first step," Prestwich said. "It shows that you can get the drug into cancer cells and kill them, and at the same dose it doesn't go into regular cells and it doesn't affect them."

He said human tests of the triple combination are at least three years away, but tests on mice will start much sooner. The doxorubicin-copolymer combination -- without the hyaluronic acid targeting mechanism -- has completed human safety trials in Europe and soon will complete initial tests of efficacy in dozens of patients.

Hyaluronic acid also can be used as a targeting mechanism in combination with other chemotherapeutic agents, Prestwich said. In unpublished research, the team used the sugar as a way to target Taxol to breast cancer cells. The technique reduced and even eliminated the cancer in mice with human tumor cells, Prestwich said. The hyaluronic acid-Taxol combination is water-soluble and can be administered easily by intravenous drip.