Nanotech News

November 14, 2005

Nanoparticle Targets Specific TNF Receptor

Using a silica nanoparticle as a starting point, researchers at the University of Stuttgart, Germany, have created a fluorescent nanoparticle capable of targeting the tumor necrosis factor (TNF) type 2 cell surface receptor, a specific receptor that may be able to trigger cell death in cancer cells. This new nanoparticle is the focus of work published in the journal Bioconjugate Chemistry by Peter Scheurich, Ph.D., and his colleagues.

TNF is a naturally occurring protein that can trigger apoptosis, or cell death, in cancer cells, but its development as an anticancer agent has been thwarted by oftentimes severe side effects. Some of these side effects may result from the fact that TNF exists in two forms in the body, and each appears to trigger distinct biological responses when it interacts with cells. One form, known as soluble TNF, circulates freely through the body. The other form, known as membrane-bound TNF, remains attached to the cells that produce it.

For reasons that are still unclear, only the membrane-bound form binds to the type 2 TNF receptor. And since nearly every study of TNF has used soluble TNF, researchers know relatively little about the TNF type 2 receptor and its unique role in triggering apoptosis. Dr. Scheurich and his colleagues wanted to create a TNF formulation that could mimic the membrane-bound form of TNF, and thus fill that knowledge gap about the type 2 receptor, and they turned to nanoparticles for a solution.

A silica nanoparticle served as the starting point of their work. The researchers first added an ultra thin fluorescent shell to the silica nanoparticle so that they could track the nanoparticle’s interactions with cells using standard confocal fluorescent microscopy. Next, they attached a genetically modified form of TNF, one that has the same biological properties as the native protein but that can also be chemically attached to the fluorescent silica nanoparticle.

Tests using human and mouse cells growing in culture showed that that TNF-nanoparticles were capable of binding to the type 2 receptor, an event observed using fluorescence microscopy. More importantly, the TNF-bearing nanoparticles were able to trigger apoptosis in cells bearing the type 2 receptor on their surfaces.

This work is detailed in a paper titled, “Tumor necrosis factor (TNF)-functionalized nanostructured particles for the stimulation of membrane TNF-specific cell responses.” This paper was published online in advance of print publication. An abstract is available at the journal’s website.
View abstract.