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Using nanoparticles to fight drug addiction
The UB researchers working on a new nanotechnology treatment for drug addiction are, clockwise from front left, Hong Ding, Indrajit Roy, Rajiv Kumar, Earl J. Bergey, Ken-Tye-Yong, Adela C. Boniou, Stanley A. Schwartz, Supriya D. Mahajan, Paras N. Prasad and Rui Hu. Photo: DOUGLAS LEVERE
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“These findings mean that in the future, we might be able to add a powerful pharmaceutical agent to the current arsenal of weapons in order to more effectively fight a whole range of substance addictions.”
A precise, new nanotechnology treatment for drug addiction may be on the horizon as the result of research conducted at UB.
Scientists in the Institute for Lasers, Photonics and Biophotonics and the Department of Medicine have developed a stable nanoparticle that delivers short RNA molecules in the brain to “silence” or turn off a gene that plays a critical role in many kinds of drug addiction.
The team’s in vitro findings were published online the week of March 23 in the Proceedings of the National Academy of Sciences.
“These findings mean that in the future, we might be able to add a powerful pharmaceutical agent to the current arsenal of weapons in order to more effectively fight a whole range of substance addictions,” said team leader Paras N. Prasad, executive director of the Institute for Lasers, Photonics and Biophotonics and SUNY Distinguished Professor in the departments of Chemistry, Physics, Electrical Engineering and Medicine.
The new approach also may be applicable to treating Parkinson’s disease, cancer and a range of other neurologic and psychiatric disorders that require certain drugs to be delivered to the brain.
At the same time, the study’s co-authors in the Department of Medicine say this highly translational research strongly suggests that the nanoparticles would be applicable to other diseases. They soon will begin studying their use in treating AIDS dementia, prostate cancer and asthma.
“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 co-author Stanley A. Schwartz, professor in the departments of Medicine, Pediatrics and Microbiology, and director of the Division of Allergy, Immunology and Rheumatology in the School of Medicine and Biomedical Sciences.
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 is a protein in the brain that facilitates addictive behaviors. Silencing the DARPP-32 gene with certain kinds of ribonucleic acid (RNA), called short interfering RNA (siRNA), can inhibit production of this protein and, thus, could help prevent drug addiction.
“When you silence this gene, the physical craving for the drug should be reduced,” said co-author Adela C. Boniou, a postdoctoral researcher in the Institute for Lasers, Photonics and Biophotonics.
The drawback has been finding a way to safely and efficiently deliver the siRNA, which is not stable by itself.
The UB researchers were successful when they combined the siRNA molecules with gold rod-shaped nanoparticles, called nanorods.
This may be the first time that siRNA molecules have been used with gold nanorods.
“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, research assistant professor in the Department of Medicine.
In addition to their biocompatibility, the gold nanorods are advantageous because they are rod-shaped, rather than spherical, allowing for more siRNA molecules to be loaded onto 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, 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 been achieved previously in other experiments.
In the next stage of the research, scientists will conduct similar experiments in vivo.
The researchers are active participants in the strategic strength in Integrated Nanostructured Systems identified in the UB 2020 planning process, which brings together researchers in the life sciences, medicine and engineering to promote interdisciplinary advancements.
Additional co-authors on the paper are Earl J. Bergey, research associate professor in chemistry; Rui Hu, senior research support specialist; and Hong Ding, Ken-Tye Yong and Rajiv Kumar, all postdoctoral associates in the Institute for Lasers, Photonics and Biophotonics.
Funding for this research was provided by the National Cancer Institute, the Kaleida Health Foundation, the John R. Oishei Foundation, the Air Force Office of Scientific Research and UB’s New York State Center of Excellence in Bioinformatics and Life Sciences.
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