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Xu Group Reports New Nanoscopy Technique

Nancy Xu

New therapeutic drugs could result from the latest advance in nanobiotechnology reported by the research group of Old Dominion University chemist and biochemist X. Nancy Xu.

She and Tao Huang, an ODU research scientist, published an article in the journal Nanoscale this month about their creation of a photostable optical nanoscopy technique - dubbed PHOTON - that allows the real-time mapping of molecular interactions at the cellular level with 1.2 nanometer resolution.

Predicting the interactions between small molecules and proteins is key to the discovery of drugs. A drug molecule can act to stymie or encourage the function of a protein or other biomolecule, resulting in a therapeutic benefit to the patient.

Small molecules, called ligands, bond with proteins to trigger various effects. "Notably, protein-ligand interactions and binding complexes play a wide variety of roles in cellular functions," Huang and Xu write in the article. "Thus, probing of protein-ligand complexes and locating of their binding sites in their native environments in real time can lead to better understanding of their roles in cellular functions."

But the binding happens at the nanoscale - between one-billionth and one-millionth of a meter - and it is very difficult for researchers to map how and where the binding happens.

That's where PHOTON can help. This far-field optical microscopy technique, used in concert with the Xu group's single-molecule nanoparticle optical biosensors (SMNOBS), enabled the ODU researchers to map individual ligand molecules and their binding sites in single protein-ligand complexes in real time. This process can be used to probe structures and functions in live organisms.

In fact, one of the drawbacks of other nanoscopy techniques can be the use of laser light as an excitation source. This often is toxic to cells and organisms that are being probed.

"In this study, we have developed a new-generation sub-diffraction imaging nanoscope, which uses a standard far-field optical microscope equipped with a multi-spectral imaging system," the article states. "The illumination source is a standing microscopic white-light illuminator (100-watt halogen lamp). No laser excitation source is needed."

The article, "Multicolored Nanometre-Resolution Mapping of Single Protein-Ligand Binding Complexes Using Far-Field Photostable Optical Nanoscopy (PHOTON)," was published June 1 on the website of Nanoscale, and will appear later in the print version. Nanoscale is a journal of the Royal Society of Chemistry in Great Britain.

Over the past decade, the Xu research group in nanobiotechnology has looked into a possible "stealth" quality for single-nanoparticle probes of living cells or for similar nanoparticle vehicles that can deliver medicine into the cells. In other words, they have been studying means by which nanoparticles can penetrate cells and accomplish their mission without harming the cells or being ejected by an efflux pumping mechanism that utilizes membrane transporters. This mechanism naturally targets foreign objects for ejection from cells.

The research group has reported success employing flecks of precious metals no longer than one-millionth of a meter as reliable probes of living cells and embryos. In this process, Xu and her colleagues have found ways to synthesize and purify silver and gold nanoparticles that will stay stable - one size, or monodisperse - over an extended period. They have also reported breakthroughs in the way they image and characterize nanoparticles using dark-field optical microscopy and spectroscopy.

The small size of the nanoparticles that have been created enables them to penetrate living organisms, but the surface area is large relative to the overall size, and this allows the particles to perform better in optical sensing and to carry a larger payload of drugs. The rainbow colors of these nanoparticles also contribute to their usefulness as probes and sensors.

Not only has the group's research advanced techniques for nanoparticle delivery of drugs, but it also has found that the nanoparticles alone, without a drug payload - particularly the large-size silver nanoparticles - may affect certain cellular functions. This means that the nanoparticles themselves could be used as nanomedicines, say, to kill cancer cells.

This article was posted on: June 10, 2011

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