Nanoparticles Sneak Drugs into Cancer Cells

A new use for Buckyball nanoparticles has been discovered -- as "passkeys" that allow drugs to enter cancer cells.

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.

"Drugs are far more effective if they're delivered through the membrane, directly into the cell," said lead researcher Andrew Barron of Rice University. "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 non-toxic pieces of protein, and we're incorporating Buckyballs as a passkey."

Buckyballs are spherical, soccer-ball-shaped molecules containing 60 carbon atoms. The passkeys that Barron and his colleagues -- pediatric specialists at Baylor College of Medicine -- developed contain a molecule called Bucky amino acid that was created in Barron's lab. Bucky amino acid, or Baa, is a marriage of Buckyballs and phenylalanine, one of the 20 essential amino acids that are the building blocks of all proteins.

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 the 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."

Barron is Rice's Charles W. Duncan Jr.-Welch Professor of Chemistry, professor of materials science and associate dean for industry interactions and technology transfer. The research appears in the Jan. 21 issue of the journal Organic and Biomolecular Chemistry; his co-authors include Rice undergraduate student Jonathan Driver and Baylor College of Medicine postdoctoral fellow Kuan Wang.

The research is supported by the Welch Foundation, the Bear Necessities Pediatric Cancer Foundation and the Hope Street Kids Foundation.

For more information, visit: www.rice.edu