Getting drugs to a tumour with nanoparticles

Side effects from cancer treatment could be greatly minimized if we can harness tiny particles

About 186,400 Canadians will be diagnosed with cancer this year, according to the Canadian Cancer Society. Despite these numbers, “every cancer is essentially a rare disease, as you get down deep in the genetic profile,” says Pieter Cullis, a professor of biochemistry and molecular biology at the University of British Columbia. He and others are working toward a future when individual patients will receive a drug therapy tailored precisely to them—delivered in tiny nanoparticles that reach right down into the cancer site.

Most cancer drugs permeate a patient’s entire body. “Only one per cent goes where it’s supposed to,” Cullis says, and the other 99 per cent can cause harmful side effects. He has developed a way to package drug molecules inside nanoparticles “one-hundredth the size of a typical cell” and made of lipids, the same material that makes up the membrane around each cell in our bodies.

These nanoparticles are designed to circulate through the system, eventually passing through the tumour. Because blood vessels at this site are newer, they’re a bit “leakier” than elsewhere in the body, Cullis says, so nanoparticles tend to accumulate there, and then release their entrapped drug molecules. “If we can get even five per cent [of the drug] to the tumour, we’ll see big benefits” and fewer unnecessary side effects, he says.

Nanoparticles are already used in cancer therapy, Cullis notes, like the drug Doxil for ovarian cancer and multiple myeloma. More are on the horizon. Celator Pharmaceuticals, which started in Vancouver, has taken two nanomedicine treatments to clinical trial: one for acute myeloid leukemia (AML) and another for colorectal cancer. The AML treatment, called CPX-351, takes standard drugs and locks them into nanoparticles at a very specific ratio. “The average survival of a patient with secondary AML, treated with a conventional chemo cocktail, is about six months,” says Celator founder Lawrence Mayer, president and head of research. “When treated with our drug, the average survival time more than doubled.” They’re about to initiate phase three clinical trials, bringing it one step closer to getting approved for sale and use.

Cullis is now working on a new application for his lipid nanoparticles. “Instead of carrying conventional anti-cancer drugs, these carry what you might term genetic drugs,” he says. The new technique packages tiny bits of RNA, which plays a role in protein synthesis and other chemical activities inside the cell. “If you could introduce those into a cell, they’ll silence one protein in that cell,” he says. It might be possible to knock out the specific, individual genes contributing to a patient’s cancer. In coming years, cancer treatments using RNA could be personalized for each patient and their disease. “It’s early days,” Cullis says, “but we’re already seeing promising results.”

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