Nanodiamonds Sparkle Delivering Drugs Without Side Effects

Northwestern University researchers have shown that nanodiamonds — much like the carbon structure as that of a sparkling 14 karat diamond but on a much smaller scale — are very effective at delivering chemotherapy drugs to cells without the negative effects associated with current drug delivery agents.

Their study, published online by the journal Nano Letters, is the first to demonstrate the use of nanodiamonds, a new class of nanomaterials, in biomedicine. In addition to delivering cancer drugs, the model could be used for other applications, such as fighting tuberculosis or viral infections, say the researchers.

Nanodiamonds promise to play a significant role in improving cancer treatment by limiting uncontrolled exposure of toxic drugs to the body. The research team reports that aggregated clusters of nanodiamonds were shown to be ideal for carrying a chemotherapy drug and shielding it from normal cells so as not to kill them, releasing the drug slowly only after it reached its cellular target.

Another advantage of the material, confirmed by a series of genetic studies also reported in the paper, is that nanodiamonds do not cause cell inflammation once the drug has been released and only bare diamonds are left. Materials currently used for drug delivery can cause inflammation, a serious complication that can predispose a patient to cancer, block the activity of cancer drugs and even promote tumor growth.

“There are a lot of materials that can deliver drugs well, but we need to look at what happens after drug delivery,” said Dean Ho, assistant professor of biomedical engineering and mechanical engineering at Northwestern’s McCormick School of Engineering and Applied Science, who led the research. “How do cells react to an artificial material left in the body? Nanodiamonds are highly ordered structures, which cells like. If they didn’t, cells would become inflamed. From a patient’s perspective, this is very important. And that’s why clinicians are interested in our work.”

“Novel drug delivery systems, such as the one being developed by Dean and his team, hold great promise in cancer therapeutics,” said Steven Rosen, M.D., director of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and Genevieve E. Teuton Professor of Medicine at Northwestern’s Feinberg School of Medicine. “We anticipate they will allow for more sophisticated means of targeting cancer cells while sparing healthy cells from a drug’s toxicity.”

To make the material effective, Ho and his colleagues manipulated single nanodiamonds, each only two nanometers in diameter, to form aggregated clusters of nanodiamonds, ranging from 50 to 100 nanometers in diameter. The drug, loaded onto the surface of the individual diamonds, is not active when the nanodiamonds are aggregated; it only becomes active when the cluster reaches its target, breaks apart and slowly releases the drug. (With a diameter of two to eight nanometers, hundreds of thousands of diamonds could fit onto the head of a pin.)

“The nanodiamond cluster provides a powerful release in a localized place — an effective but less toxic delivery method,” said co-author Eric Pierstorff, a molecular biologist and post-doctoral fellow in Ho’s research group. Because of the large amount of available surface area, the clusters can carry a large amount of drug, nearly five times the amount of drug carried by conventional materials.

Liposomes and polymersomes, both spherical nanoparticles, currently are used for drug delivery. While effective, they are essentially hollow spheres loaded with an active drug ready to kill any cells, even healthy cells that are encountered as they travel to their target. Liposomes and polymersomes also are very large, about 100 times the size of nanodiamonds — SUVs compared to the nimble nanodiamond clusters that can circulate throughout the body and penetrate cell membranes more easily.

Unlike many of the emerging nanoparticles, nanodiamonds are soluble in water, making them clinically important. “Five years ago while working in Japan, I first encountered nanodiamonds and saw it was a very soluble material,” said materials scientist Houjin Huang, lead author of the paper and also a post-doctoral fellow in Ho’s group. “I thought nanodiamonds might be useful in electronics, but I didn’t find any applications. Then I moved to Northwestern to join Dean and his team because they are capable of engineering a broad range of devices and materials that interface well with biological tissue. Here I’ve focused on using nanodiamonds for biomedical applications, where we’ve found success.

“Nanodiamonds are very special,” said Huang. “They are extremely stable, and you can do a lot of chemistry on the surface, to further functionalize them for targeting purposes. In addition to functionality, they also offer safety — the first priority to consider for clinical purposes. It’s very rare to have a nanomaterial that offers both.”

“It’s about optimizing the advantages of a material,” said Ho, a member of the Lurie Cancer Center. “Our team was the first to forge this area — applying nanodiamonds to drug delivery. We’ve talked to a lot of clinicians and described nanodiamonds and what they can do. I ask, ‘Is that useful to you?’ They reply, ‘Yes, by all means.’”

For their study, Ho and his team used living murine macrophage cells, human colorectal carcinoma cells and doxorubicin hydrochloride, a widely used chemotherapy drug. The drug was successfully loaded onto the nanodiamond clusters, which efficiently ferried the drug inside the cells. Once inside, the clusters broke up and slowly released the drug.

In the genetic studies, the researchers exposed cells to the bare nanodiamonds (no drug was present) and analyzed three genes associated with inflammation and one gene for apoptosis, or cell death, to see how the cells reacted to the foreign material. Looking into the circuitry of the cell, they found no toxicity or inflammation long term and a lack of cell death. In fact, the cells grew well in the presence of the nanodiamond material.

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Article adapted by MD Only Weblog from original press release.
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Contact: Megan Fellman
Northwestern University

Dietary calcium may prevent the spread of breast cancer to bone

A strong skeleton is less likely to be penetrated by metastasizing cancer cells, so a fortified glass of milk might be the way to block cancer’s spread, according to researchers at the ANZAC Research Institute in Concord, Australia. Using a mouse model of breast cancer metastasis, the researchers found that a calcium deficiency may increase the tendency of advanced breast cancer to target bone. Dietary calcium, they reason, might help prevent the spread of breast cancer to bone and serve as an adjuvant treatment during therapy.Their findings are presented in the Oct. 1 issue of Cancer Research, a journal of the American Association for Cancer Research.

According to the researchers, about 70 percent of patients who develop advanced breast cancer will have secondary tumors in the bone. The spread of cancer to bones leads to cellular processes that physically break down existing bone, leading to further pain and illness. In fact, the breakdown of bone and subsequent bone re-growth forms what senior author Colin R. Dunstan, Ph.D., terms a “vicious cycle” that turns bone into an environment conducive to cancer growth.

To better understand the role of bone turnover in the spread of cancer, Dunstan and his team compared the effects of a low- and high-calcium diet in mice. They found that dietary calcium deficiency – independent of the chemical factors that control turnover – was related to a significantly higher increase in cancer cell proliferation and the total proportion of bone that had been penetrated.

“These results could have implications for patients with breast cancer bone metastases or who are at high risk for developing metastatic disease,” Dunstan said. “Many older women in our community are known to be calcium deficient due to low calcium dietary intake or due to vitamin D deficiency. These women could be at increased risk for the devastating effects of bone metastases.”

According to Dunstan, his results call for further, directed clinical trials “to investigate how calcium and vitamin D status influence progression to metastatic disease, and to determine if corrections of calcium and vitamin D deficiencies are important in breast cancer patients.”

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Article adapted by MD Only Weblog from original press release.
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Contact: Greg Lester
American Association for Cancer Research

The ANZAC Research Institute study was funded by the National Health and Medical Research Council of Australia and the New South Wales Government.

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries.

AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care.

AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.