Nanoshells, buckyballs and other tools work to preserve life from the bottom up

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July 10, 2003 – Leon Hirsch started the demonstration by exposing a strip of raw skinless chicken breast to a laser. The slab remained shiny pink as a beam of near infrared light penetrated the flesh. He picked up the chicken, poked it with a syringe and injected a liquid into its center.

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Repositioned and re-exposed, the flesh under the beam began to smoke and turn white as the liquid — a formula containing gold shells each slightly larger than a polio virus — absorbed the light, heating to a high enough temperature to cook nearby cells. “It’s actually on fire now,” Hirsch said 10 seconds later, adding that the concentration of nanoshells and the light intensity were both exaggerated for the demonstration.

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In animal studies, nanoshells target cancer cells, not chicken meat, and the beam leaves the skin and healthy flesh unscathed while the shells’ heat damages only tumors. A doctoral student at Rice University, Hirsch is part of a team led by physicist Naomi Halas and bioengineer Jennifer West that is designing nanoshell particles for detecting and treating cancer. Halas and West co-founded the company Nanospectra Biosciences in 2001 in Houston to commercialize nanoshells for cancer and other medical applications.

Nanoshells are one of several nanoscale materials being developed as intravenous and topical drugs. The smorgasbord includes carbon spheres called fullerenes used by the startup C Sixty in Houston for arresting neurodegenerative diseases, and nanoparticles under study by the drug companies Advectus Life Sciences Inc. in Vancouver and American Pharmaceutical Partners in Los Angeles for treating cancers.

Some nanomaterials have a chemical makeup similar to traditional pharmaceuticals, but they perform better because of their greater surface-to-volume ratio. Others are made of biocompatible elements like gold and carbon that do extraordinarily nonbiological tasks — like neutralize cell-damaging substances or absorb or emit light for noninvasive, precise diagnostics and therapies. 

“The wonderful thing that all these beautiful bottom-up nanotechnologies are doing is allowing the conventional idea of material and device to merge,” said Halas, who invented nanoshells in the mid-1990s. “That’s perfect for some of the biological things that we’re doing.”

Girish Solanki, an industry manager for Frost and Sullivan’s Technical Insights group and author of a 2003 market report on nanotechnology, identified biotechnology and electronics as the most promising nanotech applications. But he said about 98 percent of the work is still in the research and development stage.

Metallic nanoshells’ material, size, core and shell thickness determine how each interacts with light. At about 100 nanometers, gold nanoshells can absorb or reflect light in the near infrared range. Blood and tissue, on the other hand, do not absorb near infrared light and are essentially transparent at that wavelength. Nanoshells also easily traverse the body’s circulatory system.

The Rice team gets nanoshells to congregate on cancer cells by attaching specific antibodies or peptides to the shells. The antibodies lock onto the cancer cells; the more cells the more shells accumulate. Irradiated by an external laser, the nanoshells display where they are and in what concentration. The nanoshells also act as a lens, Halas said, focusing light onto themselves for a potent and controlled heat source that can selectively destroy nearby cells.  
   
“We have a seamless integration of cancer detection and therapy,” said Halas, who recently received a $3 million innovator award to develop breast cancer applications as well. “We have identification and all-optical biopsy, but we also have the option of turning up the light a little bit and locally heating the nanoshells to a temperature (that) … will kill the cells that are in the direct vicinity of the nanoshells.”

Nanospectra Biosciences President J. Donald Payne said the cancer program could progress from animal to clinical trials in about 18 months. Further studies likely will include its collaborator, the University of Texas’ M.D. Anderson Cancer Center in Houston. The company also is likely to partner with a pharmaceutical company, which will offer experience with marketing and distribution.

“The kiss of death for most small (biotech) companies is trying to launch a product on your own,” he said. “It takes a significant amount of money.”

Like nanoshells, fullerenes look attractive for medical applications ranging from cancer and HIV treatments to free radical scavengers. Also known as buckyballs, fullerenes are made of 60 carbon atoms that form a soccer ball shape that can ferry virus-crippling compounds, for instance.

C Sixty is concentrating on what it deems its standout application as an antioxidant, taking advantage of fullerenes’ unusual ability to trap cell-damaging free radicals, said Ross Lebovitz, C Sixty’s vice president of business development. Free radicals, or atoms and molecules with unpaired electrons, are a byproduct of reactions with oxygen and other processes. They tend to be highly reactive and have been linked to the onset and progression of fatal neurodegenerative diseases like amyotrophic lateral sclerosis, commonly known as Lou Gehrig’s disease.  

“They have this flexible electron cloud that allows the fullerene to accept electrons and remain stable,” said Lebovitz, a molecular biologist and veteran entrepreneur. “In vitro and it looks like in vivo, this is one of the best antioxidants ever found.”

While fullerenes may not reverse damages from neurodegenerative diseases, they might arrest the diseases’ progression. Taken before onset, they might serve as a preventative. The company also is considering a topical fullerene-based antioxidant that could be used as a therapeutic skin care product, one that might reduce the potential cancer-causing damage of sunburn, for instance. As a topical treatment, fullerenes might face less of a regulatory hurdle and find a quicker path to the marketplace, Lebovitz said.

“We look at each opportunity,” he said. “We want to make the world better, and increase the value of our company. The two go hand in hand.” 

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