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 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.
Cleaning the impurities...
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.
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.