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Nanoparticles Designed to Form Into Tiny Drug-Catching Nets

Nathan Gianneschi (University of California in San Diego)

Nathan Gianneschi (University of California in San Diego)

Chemistry and medical researchers at University of California in San Diego designed round nanoscale particles to float through the bloodstream and change into net-like threads that accumulate at the site of tumors and help concentrate therapies. The team led by San Diego biochemistry professor Nathan Gianneschi appears online in this week’s issue of the journal Advanced Materials (paid subscription required).

The aim of the research, says Gianneschi, is to find materials that can be injected into the body with one shape, then change to another shape before they reached cancerous tumors. Some cancers produce quantities of enzymes known as matrix metalloproteinases that change the molecular composition and behavior of other proteins, often encouraging the escape of individual tumor cells that lead to the spread of cancer or metastasis.

The San Diego team harnessed this property of matrix metalloproteinases as the catalyst to change the form of the nanoparticles so they congregate at a tumor site. The researchers started with nanoparticles made of a type of detergent that either attracts or repels water at its opposite ends. With this characteristic, the nanoparticles in water self-assembled into spheres, with the water-repellent ends of the particles pointing to the inside.

When mixed with matrix metalloproteinases, the enzymes interacted with peptides on the surface of the nanoparticle balls, penetrating and opening the spheres. Once opened, the nanoparticles reassembled into threads, which then accumulated into a type of net or mesh.

Gianneschi and colleagues tested the technique on mice infected with human fibrosarcomas, a cancer of bone and other connective tissue that produces high levels of matrix metalloproteinases. The researchers inserted one of two types of fluorescent dyes, rhodamine or fluorescein, inside the nanoparticle balls. When the spheres broke down and formed into threads, the two dyes interacted to emit a specific fluorescent signal  that let the team track the change in form of the particles.

The team reports that the spheres broke down into threads and reassembled as tiny nets at the site of tumors in the test mice within one day, with the nets persisting for at least a week. The researchers say the nets did not seem to alter the tumors, not did they affect sensitive organs in the mice, such as liver or kidney.

Gianneschi says the research offers “an autonomous material that could sense its environment and change accordingly.” He and his colleagues are now developing nanoparticles carrying an infrared dye that make it possible to visualize tumors deeper in the body.

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