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Sending a rocket to the site of a cancer

Biomimetic microfluidic chips help researchers visualize the performance of nanomedicine.

Yaling Liu envisions the day when physicians can detect cancers before they are visible to modern diagnostic tools and then rocket drugs to cancerous cells in doses that treat the disease but don’t kill surrounding tissues.

It’s a big dream, and to realize it, Liu, assistant professor of mechanical engineering and mechanics, is thinking small – in nanometers. Liu is one of a growing number of researchers drawn to nanomedicine, the use of chemical particles that are an order of magnitude smaller than conventional drugs and are engineered to unleash their power directly at the site of a tumor rather than on the body as a whole. The global nanomedicine market was $73 billion in 2011 and is predicted to increase to $131 billion this year.

Nanoparticles can be designed with special coatings, or ligands, that lock into the unique chemical receptors on the surface of cancer cells. They can also be crafted to bond to tiny early-stage cancers and reveal them to diagnostic equipment. Using conventional methods, many cancers cannot be “seen” by medical scanners until they become larger and more difficult to treat.

Liu wants to engineer a “nanorocket” with drug and diagnostic components that seek out hidden cancer cells and deliver treatment at the same time. He is attempting to determine how much medication should be injected into a patient’s bloodstream so that the proper dosage is delivered to the affected region of the body.

It is not a simple relationship. The size and shape of the drug particle, the geometry of the patient’s vascular system, and the rate of blood flow at the site of the disease all influence how much of the drug will attack diseased tissue and how much of it will pass uselessly through the bloodstream.

For current nanomedicines, says Liu, as little as 3 percent of the drug injected into the bloodstream of a patient actually bonds to and attacks tumors.

Liu aims to improve those odds. In a project for the National Institutes of Health, he found that spherical nanoparticles, the easiest ones for drug makers to fabricate, bond less efficiently to diseased cells than rod- or disc-shaped particles.

Now, two years into a five-year NSF grant, Liu and his team have developed mathematical and computational models of blood flow in blood vessels of different sizes. These models can be used to predict what size and shape of particles most effectively “stick” to diseased cells and deliver a drug to various organs and tissues invaded by cancer.

Liu has developed an inexpensive way to turn his models into experiments that can be conducted on microfluidic chips using microscopic pathways to mimic the vascular system so that flow and nanoparticles can be visualized.

Compared to in vivo animal or human studies, Liu’s in vitro biomimetic microfluidic chip is “much cheaper and faster, and has a higher throughput, because we can perform a variety of experiments at the same time.”

Liu wants next to perform specific studies of lung and prostate cancer cells. Applying his modeling tools to real-world diseases will be a boon to drug makers, he says, “because every disease changes your design, and every region of the body is different.”

The ability to combine the fluid mechanics of blood flow and the biological properties of particle design with a better understanding of various cancers will allow physicians to more accurately administer effective doses of anti-cancer agents while reducing side effects.

And understanding the complex interactions between particle design and the vascular system may help pharmaceutical companies customize a line of drugs matched to patients’ age, cardiovascular health and the stage of their cancer, Liu says.

“Cancer is the number one killer of Americans,” Liu says. Will his group’s work help give patients a better chance at recovery?

“I tell my students to dream big,” Liu says. “Dream big – and you’ll always achieve something.”