Golden Bullet for Cancer? Nanoparticles Provide Targeted Version of Photothermal Therapy for Cancer
ScienceDaily (Mar 16, 2010)
In a lecture he delivered in 1906, the German physician Paul Ehrlich coined the term Zuberkugel, or "magic bullet," as shorthand for a highly targeted medical treatment.
Magic bullets, also called silver bullets, because of the folkloric belief that only silver bullets can kill supernatural creatures, remain the goal of drug development efforts today.
A team of scientists at Washington University in St. Louis is currently working on a magic bullet for cancer, a disease whose treatments are notoriously indiscriminate and nonspecific. But their bullets are gold rather than silver. Literally.
The gold bullets are gold nanocages that, when injected, selectively accumulate in tumors. When the tumors are later bathed in laser light, the surrounding tissue is barely warmed, but the nanocages convert light to heat, killing the malignant cells.
In an article just published in the journal Small, the team describes the successful photothermal treatment of tumors in mice.
The team includes Younan Xia, Ph.D., the James M. McKelvey Professor of Biomedical Engineering in the School of Engineering and Applied Science, Michael J. Welch, Ph.D., professor of radiology and developmental biology in the School of Medicine, Jingyi Chen, Ph.D., research assistant professor of biomedical engineering and Charles Glaus, Ph.D., a postdoctoral research associate in the Department of Radiology.
"We saw significant changes in tumor metabolism and histology," says Welch, "which is remarkable given that the work was exploratory, the laser 'dose' had not been maximized, and the tumors were 'passively' rather than 'actively' targeted."
Why the nanocages get hot
The nanocages themselves are harmless. "Gold salts and gold colloids have been used to treat arthritis for more than 100 years," says Welch. "People know what gold does in the body and it's inert, so we hope this is going to be a nontoxic approach."
"The key to photothermal therapy," says Xia, "is the cages' ability to efficiently absorb light and convert it to heat. "
Suspensions of the gold nanocages, which are roughly the same size as a virus particle, are not always yellow, as one would expect, but instead can be any color in the rainbow.
They are colored by something called a surface plasmon resonance. Some of the electrons in the gold are not anchored to individual atoms but instead form a free-floating electron gas, Xia explains. Light falling on these electrons can drive them to oscillate as one. This collective oscillation, the surface plasmon, picks a particular wavelength, or color, out of the incident light, and this determines the color we see.
Medieval artisans made ruby-red stained glass by mixing gold chloride into molten glass, a process that left tiny gold particles suspended in the glass, says Xia.
The resonance -- and the color -- can be tuned over a wide range of wavelengths by altering the thickness of the cages' walls. For biomedical applications, Xia's lab tunes the cages to 800 nanometers, a wavelength that falls in a window of tissue transparency that lies between 750 and 900 nanometers, in the near-infrared part of the spectrum.
Light in this sweet spot can penetrate as deep as several inches in the body (either from the skin or the interior of the gastrointestinal tract or other organ systems).
The conversion of light to heat arises from the same physical effect as the color. The resonance has two parts. At the resonant frequency, light is typically both scattered off the cages and absorbed by them. By controlling the cages' size, Xia's lab tailors them to achieve maximum absorption.
