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Xu Research Group Reports New Use of Nanoparticles Against Cancer

  • X. Nancy Xu
  • Prakash Nallathamby

Old Dominion University chemist X. Nancy Xu has been a pioneer in the use of silver nanoparticles as probes of tumor cells, and also in studies to determine if nanoparticles can deliver molecules of anti-cancer drugs into tumor cells.

Now Xu and a member of her research group, Prakash Nallathamby, are reporting new evidence that ramps up the nanoparticle-battle against cancer. Their latest peer-reviewed article explains how they have put together just the right nanoparticles with a new type of imaging system to provide evidence that the bitsy specks of silver themselves are enough to impede the growth of tumor cells.

"Study of Cytotoxic and Therapeutic Effects of Stable and Purified Silver Nanoparticles on Tumor Cells," was published online last week by the journal Nanoscale, a publication of the Royal Society of Chemistry. It will appear in the print journal later in the spring, and will be featured on the back-cover of the journal.

"It is exciting and important to find that silver nanoparticles inhibit the growth and division of the tumor cells in a dose-dependent manner, because it shows the possibility of using the cytotoxicity of the silver nanoparticles for potential therapeutic treatment of tumors," said Xu, who is a professor of chemistry and biochemistry.

The nanoparticles the researchers are working with are several nanometers (billionths of a meter) in width and have an extraordinary amount of surface space for their volume. These properties make them ideal for illuminating intracellular processes under a modern microscope, or for carrying molecules of cancer-fighting drugs into tumor cells.

But the same properties make the nanoparticles want to clump together and, therefore, to become highly unstable chemically. This presents a problem for researchers who want to determine the dose-dependent effects that nanoparticles have inside a cell. The problem might be compared to a doctor trying to evaluate an experimental medicine without being sure how pure the medicine is or how big a dose his patient has taken.

The Xu group has found ways over the last few years to synthesize and purify both silver and gold nanoparticles that will stay stable - one size, or monodisperse, as the scientists say - over an extended period.

For their latest study, Xu and Nallathamby, who will receive his doctoral degree in biomedical sciences next month, cultured mouse fibrosarcoma cells in the presence of the monodisperse silver nanoparticles and watched the nanoparticles and tumor cells with their proprietary imaging system in real-time as the nanoparticles entered into the live cells and dispersed into the cytoplasm and nuclei of the cells.

"Our results show that silver nanoparticles effectively inhibited the cell growth by disrupting cytokinesis and karyokinesis of cells (division of cells and nuclei), leading to undivided giant nuclei and multiple nuclei in single cells," the researchers write in the Nanoscale article. "The results suggest that silver nanoparticles affected the segregation of DNA (chromosomes), leading to single giant undivided nuclei in single cells. Interestingly, silver nanoparticles neither damaged DNA nor affected their replication."

"We found that purified and stable silver nanoparticles could inhibit the growth and division of tumor cells in a dose-dependent and time-dependent manner," Xu added in an interview.

Xu has been a leader worldwide over the past decade 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 has also studied 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 studies also provide new knowledge and tools to identify nanomaterials that might pose an environmental risk if they found their way out into the wild.

Last year, the group reported that their gold nanoparticles were proving to be less toxic to cells than silver nanoparticles. But this latest article shows that the researchers seem to be able to turn the toxicity of silver nanoparticles into something useful.

Xu said much work remains in order to identify the mechanisms of inhibitory effects of silver nanoparticles on the tumor cells, and to explore the finer points of using the nanoparticles as cancer therapies.

One specific hurdle remaining, she said, focuses on the pesky mechanisms that all cells have for expelling intruding specks. These efflux pumps, as they are called, work to the advantage of normal cells that are trying to protect themselves from a potentially damaging intruder. But when the cell in question is a tumor cell, and the intruder is a nanoparticle or chemotherapy drug, the efflux pump becomes a problem for the nanomedicine researcher, because the pump keeps pumping the therapeutic drugs out of tumor cells.

In general, Xu's research, which is funded by the National Science Foundation and the National Institutes of Health, explores fundamental questions posed by nanobiotechnology. She has been recognized for her achievements by two of NASA's NANO 50 awards and by the National Cancer Institute in its publication "Mission to the Inside of a Living Cell."

 

This article was posted on: April 26, 2010

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