Nanoparticle silences drug-addiction gene, promises treatment of other diseases

Scientists at the University at Buffalo (Buffalo, NY) say they have created a stable nanoparticle—a gold nanorod—that delivers short RNA molecules in the brain to "silence" expression of a gene that plays a critical role in many drug addictions. The new nanotechnology-based approach may also be applicable to treating Parkinson's disease, cancer, and a range of other neurologic and psychiatric disorders, which require certain drugs to be delivered to the brain.

The in-vitro work was a collaboration between UB's Institute for Lasers, Photonics and Biophotonics and UB's Department of Medicine. "These findings [of a study published by the Proceedings of the National Academy of Sciences] mean that in the future, we might be able to . . . more effectively fight a whole range of substance addictions," said Paras N. Prasad, Ph.D., executive director of the UB Institute for Lasers, Photonics and Biophotonics and SUNY Distinguished Professor in the departments of Chemistry, Physics, Electrical Engineering and Medicine, who led the UB team.

"The findings of this study tell us that these nanoparticles are both a safe and very efficient way of delivering to a variety of tissues highly sophisticated new drugs that turn off abnormal genes," said Stanley A. Schwartz, M.D., Ph.D., professor in the UB departments of Medicine, Pediatrics and Microbiology, director of the Division of Allergy, Immunology and Rheumatology in the UB School of Medicine and Biomedical Sciences, and a co-author on the study.

The PNAS paper describes the development of an innovative way to silence DARPP-32, a brain protein, understood to be a central "trigger" for the cascade of signals that occurs in drug addiction. DARPP-32 facilitates addictive behaviors, and short interfering RNA (siRNA) can inhibit its production. Thus, the method could help prevent or treat drug addiction.

"When you silence this gene, the physical craving for the drug should be reduced," said Adela C. Boniou, Ph.D., a post-doctoral researcher in the Institute for Lasers, Photonics and Biophotonics in the UB Department of Chemistry in the College of Arts and Sciences, and a co-author.

The drawback has been in finding a way to safely and efficiently deliver the siRNA, which is not stable by itself. But the UB researchers were successful when they combined the siRNA molecules with gold nanoparticles shaped like rods, called nanorods. This may be the first time that siRNA molecules have been used with gold nanorods, they say.

"What is unique here is that we have applied nanotechnology to therapeutic concepts directed at silencing a gene in the brain, using RNA techniques," said Supriya D. Mahajan, Ph.D., research assistant professor in the UB Department of Medicine in the School of Medicine and Biomedical Sciences.

In addition to their biocompatibility, the gold nanorods developed by the UB researchers are advantageous because they are rod-shaped rather than spherical, thus allowing for more siRNA molecules to be loaded on to their surface. This further increases their stability and allows for better penetration into cells.

"We have demonstrated that we can use these gold nanorods to stabilize the siRNA molecules, take them across the blood-brain barrier and silence the gene," said Indrajit Roy, Ph.D., deputy director for biophotonics at the institute. "The nanorods nicely address all three of these requirements."

The nanorods delivered 40 percent of the silencing RNA molecules across the blood-brain barrier model, significantly higher than the amounts that have previously been achieved in other experiments.

In the next stage of the research, the UB scientists will conduct similar experiments in vivo.

More information:
See the paper, Nanotechnology approach for drug addiction therapy: Gene silencing using delivery of gold nanorod-siRNA nanoplex in dopaminergic neurons , in the Proceedings of the National Academy of Sciences.