Nickel nanoparticles “exploit” cancer pathways

August 24, 2011 — Research by an interdisciplinary — pathologists, engineers and chemists — team of scientists at Brown University found that nickel nanoparticles activate a cellular pathway that contributes to cancer in human lung cells.

Nanoparticles offer unique properties for research and industry, but must be designed to avoid health risks, and hazards must be identified, said Agnes Kane, chair of the Department of Pathology and Laboratory Medicine in The Warren Alpert Medical School of Brown University.

Nickel nanoparticles have ions on the surface that are released inside human epithelial lung cells to jumpstart a pathway called HIF-1 alpha. This pathway normally helps trigger genes that support a cell in times of low oxygen supply, or hypoxia, but it is also known to encourage tumor cell growth.

Nickel nanoparticles "trick" the cell into reacting to nonexistent hypoxia, said Kane, who says nickel "exploits" this pathway. The pathway could give premalignant tumor cells a head start.

Figure. When human lung epithelial cells are exposed to equivalent doses of nano-sized (left) or micro-sized (right) metallic nickel particles, activated HIF-1 alpha pathways (stained green) appear mostly with the nanoparticles.

The research team, led by postdoctoral research associate Jodie Pietruska, exposed human lung cells to nanoscale particles of metallic nickel and nickel oxide, and larger microscale particles of metallic nickel. While the nanoparticles set off the HIF-1 alpha pathway, the larger metallic nickel particles did not cause the same reaction. For the same amount of metal by mass, nanoscale particles expose much more surface area, which could cause their increased chemical reactivity.

The nickel nanoparticles and nickel oxide nanoparticles react with cells differently, Pietruska said. Nickel oxide particles kill cells exposed to them quickly, which prevents any cancer-cell development. Metallic nickel particles were less likely to kill the cells, leaving the hypoxia pathway active, and possibly leading to the cell becoming cancerous. "Metallic nickel nanoparticles caused sustained activation but they were less cytotoxic," summarized Pietruska said.

The findings lead Kane to recommend nickel nanoparticle handling precautions, such as preventing airborne exposure in manufacturing. The Brown lab handled the materials under biosafety level 2 containment conditions.

While the nanoparticles were linked to cancer pathways, other biological changes would also need to happen for cancer to develop. Further research is needed on long-term exposure, and beyond the cell level.

Results were published in advance online this month in the journal Toxicological Sciences. Access it online here:

The work is supported by a National Institues of Health Superfund Research Program Grant.

In addition to Kane and Pietruska, other authors on the paper are Xinyuan Liu, chemist; Ashley Smith, doctoral student in pathobiology; Kevin McNeil, pathology lab technician; Paula Weston, histotechnician; Anatoly Zhitkovich, toxicologist; and Robert Hurt, engineer. Kane, Hurt, and Zhitkovich are associated with Brown’s Institute for Molecular and Nanoscale Innovation.

Learn more at

Nanoparticles have also been shown to fight cancer at Brown.


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