February 6, 2006
Gold Nanoparticle-Virus Networks Work as Intracellular Sensors and Targeting Agents
Researchers at The University of Texas M. D. Anderson Cancer Center report that they have created a way for viral and gold particles to "directly assemble" and potentially seek out and treat disease where it resides in the body. Their study, published in the Proceedings of the National Academy of Science USA, demonstrates how to use biologically compatible materials to fabricate a "nanoshuttle" that can be harnessed to viral particles to precisely home to disease wherever it hides.
Once there, the nanoshuttle can perform a variety of functions. This study defines how assembled particles of gold—a metal that is not rejected by the body—could possibly be "tuned" to destroy tissue or emit signals that can be detected by imaging devices. The system also can be adapted to form a flexible scaffold that can carry drugs, genes or even cradle restorative stem cells.
"Gold is a perfect metal to perform these different functions, and scientists have been trying to find a way to target such particles to specific organs or tissues, but it has been extremely difficult," says the co-leader of the study, Renata Pasqualini, Ph.D. "Instead of taking the usual approach by using a synthetic molecule or polymer, we have found a way to mix a 'genetically programmable' nanoparticle with a biologically compatible metal that together target specific locations in the body."
These nanoplatforms and scaffolds have not as yet been tested in animal models or humans. Nonetheless, this study is the first to show how, in a laboratory, gold and phage (viruses that infect only bacteria) can combine and build a matrix that can support stem cells.
The disease-finding capability of these scaffolds is due to the specially engineered virus that displays a peptide that matches a specific protein receptor on the tissue or tumor of interest. This homing technique was pioneered by the lead authors on the current study, Pasqualini and Wadih Arap, M.D., Ph.D., of the M. D. Anderson Cancer Center. Their previous work revealed that the human vascular system contains unique molecular addresses, depending on the site of an organ or tissue, and that blood vessels also acquire abnormal signatures on diseased organs. They were the first to attach such unique vascular "zip codes" to phage, engineering them in such a way that these viral particles would go to these target addresses.
The advance reported in the current paper was only made possible, Pasqualini says, because she and Arap invited chemist Glauco Souza, Ph.D., another colleague at M. D. Anderson Cancer Center, to work on the problem. "This was truly a multidisciplinary approach, and it brings together something chemists, physicists and biologists have been trying to do, separately and unsuccessfully, for a long time," Souza says.
This work is detailed in a paper titled, “Networks of gold nanoparticles and bacteriophage as biological sensors and cell-targeting agents.” Shuming Nie, Ph.D., is the principal investigator of the Emory-Georgia Tech Nanotechnology Center for Personalized and Predictive Oncology. Researchers from The Burnham Institute and George Washington University also participated in this study. This paper is available free through PubMed Central.