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A silver bullet for tumours?
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A lot of research in recent years has focused on the issue of targeting therapies to tumours and sparing surrounding healthy cells and tissues. Nanoparticles have emerged as a potential vehicle for this kind of targeted delivery. In a new study in the journal Nature Materials a nanoparticle with certain unique properties is described which allows targeting of tumour cells, ready visualisation of internalised nanoparticles and breakdown of non-internalised and potentially toxic nanoparticles for elimination. These silver nanoparticles were developed in the laboratory of Prof Erkki Ruoslahti of the University of California in Santa Barbara.

The research team exploited a phenomenon called plasmonics when developing the nanoparticles in which nanostructured materials including gold and silver resonate in light such that their electromagnetic fields are concentrated near the surface. This allows enhancement of the fluorescence of dyes used to label the nanoprobes, making them much more readily detectable. In the current study, the researchers designed an etching technique in which biocompatible materials were used to break down and remove non-internalised silver nanoparticles with minimum toxicity. This left only the internalised pool for imaging and quantification. Lead author Dr Gary Braun explains: "The disassembly is an interesting concept for creating drugs that respond to a certain stimulus…It also minimizes the off-target toxicity by breaking down the excess nanoparticles so they can then be cleared through the kidneys."

The particles were spherical in shape and were coated with a peptide that enabled it to be targeted to tumour cells. While some drugs can penetrate the cell membrane, others cannot, for example RNA and DNA genetic drugs. This is where nanoparticle carriers that can be internalised in the tumour cell come in. Dr Braun explains: "This typically requires a nanoparticle carrier to protect the drug and carry it into the cell…And that's what we measured: the internalization of a carrier via endocytosis." The intense fluorescence of the plasmonic nanoparticles made internalisation readily detectable while the etching technology meant that excess nanoparticles could be broken down and expelled by the kidneys.

The peptide coating of the core nanoparticles has the potential to be varied to allow different types of tumours or bacterial organisms to be targeted. Senior author Prof Ruoshlati concludes: "These new nanoparticles have some remarkable properties that have already proven useful as a tool in our work that relates to targeted drug delivery into tumours…They also have potential applications in combating infections. Dangerous infections caused by bacteria that are resistant to all antibiotics are getting more common, and new approaches to deal with this problem are desperately needed. Silver is a locally used antibacterial agent and our targeting technology may make it possible to use silver nanoparticles in treating infections anywhere in the body."

Figure: Prostate cancer cells were targeted by two separate silver nanoparticles (red and green), while the cell nucleus was labeled in blueusing Hoescht dye. (UCSB)


Sources

Etchable plasmonic nanoparticle probes to image and quantify cellular internalization. Braun, G. B., Friman, T., Pang, H.-B., Pallaoro, A., de Mendoza, T. H., Willmore, A.-M. A., Kotamraju, V. R., Mann, A. P., She, Z.-G., Sugahara, K. N., Reich, N. O., Teesalu, T., and Ruoslahti, E. (2014). (8 June 2014), doi:10.1038/nmat3982

Press release: UC Santa Barbara, available from: http://www.eurekalert.org/pub_releases/2...060614.php

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