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Nanoparticles enable optical and MR imaging of cancer cells

BioPhotonics
Sep 2007
David L. Shenkenberg

Wenbin Lin and colleagues at the University of North Carolina at Chapel Hill have developed nanoparticles that target cancer and enable both optical and magnetic resonance imaging. Lin said that using both imaging modalities could synergize their respective strengths. MRI offers high contrast but is expensive, whereas optical imaging is inexpensive but has yet to be used widely in the clinic because it provides lower spatial resolution.

Prior to the current experiment, the researchers had developed hybrid silica nanoparticles that had a core consisting of fluorescent [Ru(bpy3)]Cl2 with an outer layer of paramagnetic gadolinium-based nanoparticles, commonly used MRI contrast agents. The fluorophore is relatively nontoxic, and it has greater photostability than conventional organic fluorophores such as fluorescein isothiocyanate.

BNselfassemble_Fig-1_partic.jpg
This transmission electron microscopy image shows nanoparticles containing a contrast agent and fluorophore. Reprinted with permission of JACS.

In the current experiment, the researchers alternately added positively charged gadolinium-based polymers and negatively charged polystyrenesulfonate to the previously developed nanoparticles. The attraction of the opposite charges caused the gadolinium-based polymers and polystyrenesulfonate to self-assemble in layers around the hybrid silica nanoparticles. Lin said that, although layer-by-layer self-assembly so far has found limited functional applications, the researchers believed that it would increase the access of water to gadolinium and, thus, increase the MRI contrast.

BNselfassemble_Fig-2_diagra.jpg
This diagram shows the structure of the nanoparticles, including polystyrenesulfonate (green), gadolinium-based polymer (blue), targeting peptide (Ks and RGD), and fluorophore (red) and gadolinium-based coating layer (gray).

They used the nanoparticles to label cancer cells in vitro and imaged the cells using an MRI scanner. They determined that the layers of gadolinium and polystyrenesulfonate increased the contrast of the magnetic resonance images, resulting in more clearly defined features than without the additional layers, just as they had predicted.

Because they believed that it would increase image contrast, the researchers next added a peptide sequence known to target cancer cells, and they performed both MRI and laser scanning confocal imaging. They discovered that targeting increased the contrast of the magnetic resonance images as well as the fluorescence signals in the confocal images.

The researchers noted that their strategy will be broadly useful for imaging diseases, not only cancer. Lin said that they already are using similar nanoparticles for in vivo imaging in animal models of human diseases such as inflammatory arthritis and cancer, and he said that they plan to perform human testing if the animal experiments are successful.

Journal of the American Chemical Society, July 25, 2007, pp. 8962-8963.


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