Buckyballs deliver drugs to cancer cells

Key Discovery
Buckyballs deliver drugs to cancer cells

BY JADE BOYD
Rice News staff

Rice University scientists and Baylor College of Medicine pediatric specialists have discovered a new way to use Rice’s famed buckyball nanoparticles as passkeys that allow drugs to enter cancer cells.

The research, which appears in the Jan. 21 issue of the journal Organic and Biomolecular Chemistry, is the latest to capitalize on the development of a unique molecule called ”bucky amino acid,” or BAA. BAA is a buckyball-containing amino acid that is based on pheylalanine, one of the 20 essential amino acids from which all proteins are made. BAA was created in the laboratory of Andrew Barron, the Charles W. Duncan Jr.-Welch Professor of Chemistry, professor of materials science and associate dean for industry interactions and technology transfer.

”Drugs are far more effective if they’re delivered through the membrane, directly into the cell,” Barron said of the pediatric cancer study. ”Viruses, which are often toxic, long ago developed ways of sneaking through cell walls. While we’re mimicking some techniques used by viruses, we’re using nontoxic pieces of protein, and we’re incorporating buckyballs as a passkey.”

All living cells defend themselves by walling off the outside world. Cell walls, or membranes, form a protective cocoon around the cell’s inner machinery and its DNA blueprints.

Barron’s graduate student, Jianzhong Yang, developed several different BAA-containing peptides, or slivers of protein containing about a dozen or so amino acids. In their natural form, with pheylalanine as a link in their chain, these peptides did not pass through cell walls.

Barron’s group collaborated with Yang’s brother, Baylor College of Medicine Assistant Professor Jianhua Yang at Texas Children’s Cancer Center, and found the BAA-containing peptides could mimick viral proteins and pass through the walls of cancer cells. The peptides were found effective at penetrating the defenses of both liver cancer cells and neuroblastoma cells.

”Neuroblastoma is the most common extracranial solid tumor in children, and it is responsible for about 15 percent of pediatric cancer deaths,” said Jianhua Yang. ”Our findings are significant because neuroblastoma cells are well-known for their difficulty in transfection through the cell membrane.”

The research was supported by the Welch Foundation, the Bear Necessities Pediatric Cancer Foundation and the Hope Street Kids Foundation. Co-authors on the study include Rice undergraduate student Jonathan Driver and Baylor College of Medicine postdoctoral fellow Kuan Wang.

A second BAA-related study appeared in the Jan. 10 issue of the American Chemical Society’s journal Nano Letters. In that study, Barron and Jianzhong Yang partnered with North Carolina State University toxicologists and found that repetitive movement can speed the uptake of nanoparticles through the skin.

In that study, a BAA solution was placed on small sections of pig skin. In some experiments, the skin was held still and in others it was flexed for either an hour or an hour and a half. Measurements were taken eight hours after exposure and 24 hours after exposure.

The team found that the more the skin was flexed, the more buckyballs it took up and the deeper they penetrated. Penetration was also found to be deeper after 24 hours than after just eight.

”Our results confirm that repetitive motion can speed the passage of nanoparticles through the skin,” said Nancy Monteiro-Riviere, professor of investigative dermatology and toxicology at NC State. ”As more nanoparticles find their way into the workplace and consumer goods, and as scientists look for innovative ways to use nanoparticles to deliver drugs into the body, it is critical that the nanoscience community identify these types of external exposure factors.”

The toxicological study was funded by the Environmental Protection Agency, the National Academies Keck Futures Initiative and the Welch Foundation. Co-authors included NC State graduate student Jillian Rouse.