Famous Poison Kills Cancer in Nano Doses

How nanobins destroy cancer

(1). Nanobins slip through leaky vasculature and enter tumor cells

(2). Nanobins release arsenic inside the tumor cells

(3). Arsenic kills the tumor cells without harming healthy tissue

Credit: Northwestern University

“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.

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 lung cancer cells. 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

Credit: Northwestern University

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 cells lure these decorated nanobins to their surface, eager to acquire the attached decorations. Then, the cancer cells “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.”