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Gold particles could deliver cancer drugs

A longtime challenge has been delivering medicine in high enough doses to kill cancer cells while not harming the patient.

CytImmune

A longtime challenge has been delivering medicine in high enough doses to kill cancer cells while not harming the patient.

The pharmaceutical giant AstraZeneca­ is expected to announce this week that its oncology unit in Waltham is collaborating with a Maryland company to develop an innovative cancer therapy. The proposed treatment involves delivering powerful cancer drugs on the backs of gold nanoparticles made by CytImmune, of Rockville, Md., that are so tiny 5,000 of them can fit in the width of a human hair.

At that size, the gold flecks make a particularly good vehicle because they can easily carry other molecules, like cancer drugs. They are also believed safe to use in the body.

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The gold nanoparticles may solve a longtime challenge facing cancer drug developers: delivering medicine in high enough doses to kill the cancer cells but not the patient, said Dr. Steven K. Libutti, director­ of the Montefiore Einstein Center for Cancer Care in New York.

That often means finding the right vehicle to deliver the drug directly to the cancer cells, a promise offered by nanomedicine because the particles are so small they bypass healthy tissue but get trapped in tumors.

“We are in kind of a revolution now,” said Dan Peer, head of the laboratory of nanomedicine at Tel Aviv University. “We’re going to witness more and more nanoparticles as vehicles for chemotherapy.”

CytImmune has been developing a gold nanoparticle that will be particularly effective at seeking out and killing tumor cells, without causing devastating side effects.

“If we can reduce the tumors where they are, we can significantly reduce or completely eliminate the need for surgeries, which would reduce time in hospitals. I would posit that this would reduce health care costs,” said CytImmune’s chief executive, Lawrence ­Tamarkin.

Although gold as an investment commodity has been steadily posting record prices, there is so little used in the making of the medicine that “the bottle costs more than the nanoparticles in the bottle,” he added.

Each CytImmune gold particle is designed to carry three elements: a drug called TNF that is too toxic to be delivered in more conventional ways; a second cancer drug from AstraZeneca­ that the two companies hope will combine with TNF to kill more cancer cells; and a molecule of ethylene glycol designed to disguise the treatment from the body’s immune system.

The treatment is called 6091, and the TNF gives it an edge over other nanoparticles, Tamarkin said, by making the drug better at finding and killing tumor cells. The TNF drug, or tumor necrosis factor, seems to improve the nanoparticle’s homing mechanism for tumor cells. Early research suggests that gold molecules with TNF accumulate better in tumor cells than those without the drug, Libutti said.

TNF was considered extremely promising as a cancer drug back in the 1980s, based largely on animal data. But when it was tried on its own in people, the outcome was bad: “The dose at which half the patients died was lower than effective dose” needed to treat the cancer, said Libutti, who has led clinical trials that use CytImmune’s compounds.

Tamarkin said the TNF works by binding to and killing cells that make up the tumor’s blood vessels. This deprives the tumor of needed blood supply and creates openings for chemotherapy drugs to get into the tumor, he said.

The “eureka observation,” Libutti said, was that attaching TNF to gold particles actually made the drug less toxic. It could be given at higher doses, making it more effective at killing cancer cells, but less dangerous to healthy ones, he said.

Many drug companies have cancer drugs on their shelves that are too toxic to deliver to the whole body, but might be less dangerous if paired with gold and targeted directly at the tumor, Libutti said.

AstraZeneca has spent a year investigating different targeted cancer therapies and chose CytImmune’s approach as one of several investments in the area.

“CytImmune is one of the most exciting ones,” said Detlev­ Biniszkiewicz, vice president for strategy in AstraZeneca’s oncology innovative medicines unit.

The Maryland company has expertise that AstraZeneca can benefit from, he said, while the bigger company can help speed up the drug development process.

“Together we might do something nice,” Biniszkiewicz said. “Pharma needs to be more innovative. We’re trying.”

Libutti said he is about to launch a new phase of research, giving patients the 6091 nanoparticle drug along with a regimen of Taxol, a chemotherapy commonly used against breast, ovarian and lung cancers, to see if the combination improves Taxol’s effectiveness­.

He is submitting a grant proposal for early clinical research to put Taxol directly onto the 6091 molecule to see if that works even better.

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