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Saturday, January 19, 2008

Solid gold nanoparticles have long been used to treat rheumatoid arthritis and treating various types of cancer.

Gold Nanoparticles Shine Brightly in Tumors
Solid gold nanoparticles have long been used to treat rheumatoid arthritis and more recently have shown promise in treating various types of cancer. Now, thanks to work by Shuming Nie, Ph.D., and his colleagues at the Emory-Georgia Tech Nanotechnology Center for Personalized and Predictive Oncology, these same nanoparticles could serve as a powerful tumor-homing beacon for detecting microscopic tumors or even individual malignant cells. The researchers report their findings in the journal Nature Biotechnology.

Starting with colloidal gold—a commercially available suspension of gold nanoparticles—the investigators attached one of several positively charged organic dye molecules to the particles’ surfaces. The chosen dye molecules absorb and emit light in the near-infrared region of the spectrum, a portion of the spectrum that passes unabsorbed through biological tissues.

The researchers then added a nanometer-thick layer of polyethylene glycol (PEG) to render the construct biocompatible. To their surprise, this coating also made the resulting optical probe incredibly stable under even harsh chemical conditions. More importantly, the optical properties of both the gold nanoparticles and the dye molecules remained constant even after application of the coating. These particles were also nontoxic to cells over periods as long as 6 days.

These initial experiments showed that the coated gold nanoparticles could serve as potent imaging agents for studies of cancer cells, but the real goal of this project was to develop targeted in vivo imaging agents for detecting cancer in humans.

To prepare a targeted nanoparticle, the researchers used a version of PEG to which they could chemically link an antibody that binds to epidermal growth factor receptor (EGFR), a molecule overexpressed on many types of tumors. Antibodies and small molecules that bind to EGFR have been approved to treat non-small cell lung cancer.

The investigators injected the targeted nanoparticles into mice with EGFR-positive human head and neck carcinomas and obtained SERS spectra 5 hours later. As control experiments, the researchers injected matching mice with the untargeted nanoparticle. The unique optical spectra of the nanoparticles were easily detected in both sets of animals, but only the targeted nanoparticles accumulated in tumors. In contrast, the untargeted nanoparticles accumulated largely in the liver.

This work, which was supported by the National Cancer Institute’s (NCI) Alliance for Nanotechnology in Cancer, is detailed in the paper “In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags.” An abstract of this paper is available through PubMed.

Organizing Gold Nanoparticles with DNA

Tiny billionth-of-a-meter sized clusters of gold atoms — gold “nanoparticles” — are being widely studied by scientists. They have many useful potential applications, from carriers for cancer-treatment drugs to digital data storage. But many of these applications, particularly those in electronics, require that the nanoparticles form ordered arrays that can be hard to achieve. At Arizona State University (ASU), researchers have discovered that grids made of DNA strands are excellent templates for neatly organizing gold nanoparticles.
“The collective properties of nanoparticles are heavily dependent on how the particles are grouped. Achieving an even spacing between the particles is particularly important, but can be difficult,” said the study’s lead scientist, ASU chemist Hao Yan. “However, when deposited onto a DNA grid the particles fall neatly into patterns with little effort on our part.”
Yan and his research group used gold nanoparticles that were five nanometers in diameter. Rather than being bare, the particles were coated with a layer of DNA “pieces,” called “T15 sequences,” which radiated from the particles’ surfaces like arms. The scientists then deposited the particles onto lattices formed by two types of cross-shaped DNA “tiles”, “A” tiles and “B” tiles, that bind together in an alternating fashion to form the DNA grid.

At regular intervals, each A tile contained a short single strand (called an “A15” strand) that protruded out of the tile surface. These strands served as tethering points for the T15-coated nanoparticles, allowing the particles to stick to the DNA surface, a bit like DNA-nanoparticle “Velcro.”

This configuration caused the nanoparticles to “self assemble” into a square pattern — each particle sitting on one A tile — with a nearly constant particle-particle distance of about 38 nanometers. The group confirmed this using an atomic force microscope, a very powerful imaging device.

However, this result, while welcomed by the scientists, wasn’t exactly what they expected.

“We were pleased that the gold nanoparticles formed a very regular square pattern, but it wasn’t quite the pattern we thought we’d see,” said Yan. “If you picture nine DNA tiles forming a square, we predicted that five particles would be organized on the square — one on each corner and one in the middle. But the pattern we observed lacked that middle particle.”

The scientists guess that this is due to the T15 sequence layer, which effectively increases the diameter of each nanoparticle and, moreover, makes each particle highly negatively charged. As a result, the nanoparticles repel each other if they are too close together, which limits the minimum particle-particle distance. Therefore, a particle located at the center of the square would violate this limit.

In future research, Yan and may try to use this organization method to form more complex nanoparticle arrays, such as denser patterns or patterns of different shapes, by altering the particles’ DNA coating.

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