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Gold Over Silver is Theme of Nanoparticle Findings by Xu Research Group

Biotechnology researchers working with nanoparticle bio-probes at Old Dominion University have come up with one more reason why gold is trading at nearly $1,000 an ounce this month, while the same weight of silver can be had for $15.

X. Nancy Xu, professor of chemistry and biochemistry, and several members of her research group reported Aug. 28 in the online Nanoscale, a peer-reviewed journal of the Royal Society of Chemistry, that gold nanoparticles are proving to be safer probes of living embryos than the silver nanoparticles the group has created and tested in the past.

Lauren Browning and Kerry Lee, Ph.D. students in the research group, are the lead authors of the paper titled "Random Walk of Single Gold Nanoparticles in Zebra Fish Embryos Leading to Stochastic Toxic Effects on Embryonic Developments." Other authors are graduate student Prakash Nallathamby, undergraduate student Jill Lowman, and research scientist Tao Huang. The paper will be published in the print version of Nanoscale later this month.

The authors note that the use of gold nanoparticles is centuries old. For example, medieval craftsmen used gold dust to create stained glass windows, therefore the magnificent interactions that gold has with light are well known. Gold also possesses inert chemical properties that make it both stable and biocompatible, which this latest research by ODU chemists is bearing out.

For nearly a decade, Xu has been a leader worldwide in a nascent biotechnology field that is investigating the use of nanoparticles in the fight against cancer and for other medical purposes. The field has come to be called nanomedicine. The Xu group has shown that these miniscule agents can infiltrate living cells or embryos and literally light them up, allowing scrutiny of life processes. To this end, her group must first study the biocompatibility and potential toxicity of nanoparticles, aiming to rationally design biocompatible nanoparticle probes that will not harm the cells or living organisms that are under investigation by the nanoprobes. Their study also provide new knowledge and tools to identify nanomaterials that might pose an environmental risk if they found their way out into the wild.

In general, the work, which is funded by the National Science Foundation and the National Institutes of Health, explores fundamental questions posed by nanobiotechnology.

In research reported over the past two years, the Xu group has been able to create smaller and smaller silver nanoparticles that can be used as biosensors to study molecular-level functions of a key protein inside live cells. The protein mediates a variety of biological effects, such as immune regulation, antitumor activity and infection resistance.

Also reported have been new ways to synthesize stable silver nanoparticles that are particularly well suited for complex probes of live zebra fish embryos. These new monodisperse-or size-consistent-nanoparticles remain stable (non-aggregated) in solution for months, and they do not photobleached under white light illumination. The researchers have been able to deploy these tiny probes to simultaneously image multiple nanoenvironments of live zebra fish embryos in real time.

In 2007, when the Xu group first reported its study of nanoparticle probes of zebra fish embryos, they included findings of dose-dependent toxicity of silver nanoparticles on embryonic development. The researchers found that in relatively low concentrations the single-nanoparticle probes are not toxic to embryos, but that toxicity increases as concentrations increase. The results, they said, suggested serious environmental consequences for any major leak of silver nanoparticles into the wild.

One aim of their work was to develop an in vivo system to screen the biocompatibility and toxicity of nanomaterials, and with zebra fish embryos they found just such an in vivo system.

Zebra fish and humans have genetic and drug-target-site similarities that make the fish particularly useful in research concerning the treatment of human diseases. In addition, zebra fish are small, inexpensive and well suited for whole animal studies.

Xu said another advantage for researchers is that the zebra fish's early embryonic development completes within 120 hours with well-characterized developmental stages. The embryos are transparent and develop outside of their mothers, permitting direct visual detection of pathological embryonic death, maldevelopment phenotypes and study of real-time transport and effects of nanoparticles in vivo.

In its latest study, the group reports successful synthesis and characterization of stable and pure gold nanoparticles that have the same size and surface functional groups of their silver nanoparticles, allowing the researchers to compare the effect of chemical properties of gold and silver nanoparticles on living organisms. These gold nanoparticles can passively diffuse into the chorionic space of the embryos like their silver counterparts, and begin the "random walk" that is referenced in the paper's title.

Unlike the silver nanoparticles, however, the researchers found no direct connection between the concentration of gold nanoparticles inside the embryos and the normal development of the embryo.

About 74 percent of the tested embryos developed normally, while the remainder either died or were deformed. Histological tissue sample preparation and imaging developed by the group showed that the fate of the embryos did not seem to be determined by the locations of nanoparticles within the embryos. This is the "stochastic" outcome of the title, meaning that toxicity seemed to occur randomly, in the same vein as the random roaming of the nanoparticles.

"These results show that gold nanoparticles are much more biocompatible with (or less toxic to) the embryos than the silver nanoparticles that we reported previously, suggesting that they are better suited as biocompatible probes for imaging living organisms (embryos) in vivo," the paper states. "The results provide powerful evidence that the biocompatibility and toxicity of nanoparticles are highly dependent on their chemical properties, and that the embryos can serve as effective in-vivo assays to screen their biocompatibility."

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