Fighting Drug Addiction By Targetting The Brain With Nanoparticles

A precise, new nanotechnology treatment for drug
addiction may be on the horizon as the result of research conducted at
the University at Buffalo.



Scientists in UB's Institute for Lasers, Photonics and Biophotonics and
UB's 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 UB 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 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 new approach developed by the UB researchers also may 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.



At the same time, the study's co-authors in the UB Department of
Medicine say this highly translational research strongly suggests that
the nanoparticles would be applicable to other diseases. They will soon
begin to study 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
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 is a protein in the brain that facilitates addictive
behaviors. Silencing of 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 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.



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.



"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.



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, Ph.D., research
associate professor in chemistry; Rui Hu, senior research support
specialist, and Hong Ding, Ph.D., Ken-Tye Yong, Ph.D., and Rajiv Kumar,
Ph.D., 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.



The University at Buffalo is a premier research-intensive public
university, a flagship institution in the State University of New York
system and its largest and most comprehensive campus. UB's more than
28,000 students pursue their academic interests through more than 300
undergraduate, graduate and professional degree programs. Founded in
1846, the University at Buffalo is a member of the Association of
American Universities.

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