Fighting cancer with a famous poison

May 30, 2018 by Clare Milliken, Northwestern University
Fighting cancer with a famous poison
(1) Nanobins slip through leaky vasculature and enter tumor cells. (2) Nanobins release arsenic inside the tumor cells. Credit: Northwestern University

"Some of the most potent cancer drugs ever made include metals and other inorganic compounds."

Chemist Tom O'Halloran is a world-renowned expert on inorganic compounds—metals, specifically—and how these compounds function in the body. He believes certain inorganic elements and compounds could be used more broadly to kill .

Like . Arsenic is known more for its use as a poison than as a cancer drug. Arsenic poisoning is said to have killed Napoleon Bonaparte and Simon Bolivar. And paradoxically, is associated with an increased risk of cancer.

Yet low doses of have shown a 95 percent remission rate in acute promyelocytic leukemia (APL), a type of blood cancer. Arsenic can shut down the growth of other cancers as well, O'Halloran says, but conventional arsenic delivery methods have not been successful in solid tumors in the breast, lung, ovaries and elsewhere.

"What limits arsenic's broader application in cancer is its toxicity," O'Halloran says. "So, we asked whether we could control that toxicity but still allow its destructive effect to manifest only in cancer cells."

Repurposing a poison

Fighting cancer with a famous poison
(3) Arsenic kills the tumor cells without harming healthy tissue. Credit: Northwestern University

To do this, O'Halloran and his team put insoluble particles of arsenic into a liposome, a tiny droplet of fat about one-hundredth the width of a human hair, creating what they called a "nanobin." These nanobins, when injected into the bloodstream, release arsenic only once they reach cancer cells. Healthy cells remain unscathed. But how?

To understand how nanobins work, O'Halloran says, it's necessary to understand biology. Cancer cells need to recruit a source of oxygen and nutrients in order to survive and grow. Through a process called angiogenesis, tumors send out signals that stimulate blood vessels to grow toward, in and around the tumor. Those new vessels, unlike others throughout the body, are leaky, with gaps and holes several hundred nanometers in diameter. These new vessels don't leak red blood cells, which are too big to move through nanometer-sized holes, but nanobins can slip through the gaps to collect in the tumor.

"The tumors start collecting the nanobins in ways that normal tissue doesn't, building up the concentration of these arsenic-loaded liposomes in the tumor," O'Halloran says.

But once the nanobins collect in the tumor, how does the arsenic come out? Again, O'Halloran uses cancer biology to his advantage. Due to the way cancer cells process nutrients and make energy, they are slightly more acidic than normal cells. That acid helps dissolve the arsenic particles inside the nanobins, releasing the active drug inside the tumor.

"The acidic character of the tumor helps it grow and proliferate, which is something we can take advantage of with nanobins," O'Halloran says.

O'Halloran has found a way to exploit the unique features of tumors to smuggle arsenic directly into cancer cells: the leakiness of the newly created blood vessels helps nanobins collect in the tumor, and the acidic interior of the tumor coaxes the arsenic out.

Fighting cancer with a famous poison
O’Halloran collaborates with research associate Haimei Chen in his lab. Credit: Northwestern University

Working in collaboration with the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, O'Halloran's team has shown in animal models that nanobin injections effectively kill breast, ovarian and . O'Halloran and his collaborator Teresa K. Woodruff, chief of reproductive biology research at the Feinberg School of Medicine, showed that unlike other drug regimens, nanobin treatment is "ferto-protective," preserving fertility while killing cancer.

"I think this is really critical for drug delivery and development," O'Halloran says. "In addition to fertility concerns, heart toxicities are common with cancer drugs, and we often don't deal with them until the late stages of drug discovery. Delivery mechanisms like nanobins could help protect healthy tissue from these and other harmful effects of cancer treatment."

Trojan horse in the brain

O'Halloran is now testing a way to track nanobins inside the body, attaching to their surface certain molecules that cancer needs to survive. These molecule "decorations" transform each nanobin into a Trojan horse, O'Halloran says. Cancer lure these decorated nanobins to their surface, eager to acquire the attached decorations. Then, the "open the door and bring the lipid vessel—the whole kit and caboodle—into the cell," O'Halloran says.

The results of this work have been striking. These decorated nanobins were able to cross the blood-brain barrier, release the arsenic and kill brain tumors that metastasized from the breast. Buoyed by these findings, and working with Northwestern Feinberg School of Medicine neurologist C. David James, O'Halloran now has his sights set on glioblastoma, a notoriously aggressive brain cancer with virtually no effective treatment.

"It's abundantly clear that we need completely new methods to try to shut down cancer proliferation," O'Halloran says. "We're very excited that our work could pave the way for new types of treatments for brain, breast and other very resistant cancers."

Explore further: New chemo drug gentler on fertility, tougher on cancer

Related Stories

New chemo drug gentler on fertility, tougher on cancer

March 22, 2013
A new gentler chemotherapy drug in the form of nanoparticles has been designed by Northwestern Medicine® scientists to be less toxic to a young woman's fertility but extra tough on cancer. This is the first cancer drug tested ...

Scientists explore molecular link between arsenic exposure and lung cancer

July 25, 2012
Arsenic is a natural element in the environment, sometimes found in air, soil and water. Arsenic contaminated water is a global threat, currently affecting more than 100 million people. Both genetic and epigenetic changes ...

Therapeutic form of arsenic is a potential treatment for deadly type of brain cancer

October 17, 2017
From Sherlock Holmes to Agatha Christie, arsenic is often the poison of choice in popular whodunits. But in ultra-low dosage, and in the right form, this naturally occurring chemical element can be a potent force against ...

Recommended for you

Ovarian cancer cells switched off by 'unusual' mechanism

June 19, 2018
Scientists at the Ovarian Cancer Action Research Centre at Imperial College London have discovered a mechanism that deactivates ovarian cancer cells.

Breast cancer could be prevented by targeting epigenetic proteins, study suggests

June 19, 2018
Researchers at the Princess Margaret Cancer Centre in Toronto have discovered that epigenetic proteins promote the proliferation of mammary gland stem cells in response to the sex hormone progesterone. The study, which will ...

Targeting the engine room of the cancer cell

June 18, 2018
Researchers at Columbia University Irving Medical Center (CUIMC) have developed a highly innovative computational framework that can support personalized cancer treatment by matching individual tumors with the drugs or drug ...

Study suggests well-known growth suppressor actually fuels lethal brain cancers

June 18, 2018
Scientists report finding a potentially promising treatment target for aggressive and deadly high-grade brain cancers like glioblastoma. But they also say the current lack of a drug that hits the molecular target keeps it ...

Researchers create novel combination as potential therapy for high-risk neuroblastoma

June 18, 2018
Researchers at VCU Massey Cancer Center in Richmond, Virginia, have identified a promising target to reverse the development of high-risk neuroblastoma and potentially inform the creation of novel combination therapies for ...

Genomics offers new treatment options for infants with range of soft tissue tumors

June 18, 2018
The genetic causes of a group of related infant cancers have been discovered by scientists at the Wellcome Sanger Institute, the University of Wuerzburg and their collaborators. Whole genome sequencing of tumours revealed ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.