A neuron in primary neuronal cultures generated from a brain of a fruit fly is aglow with ORMOSIL, a nanoparticle that holds potential for delivering drugs to the brain. Image: Shermali Gunawardena andPLoS One. |
In the images of fruit flies, clusters of neurons are all lit
up, forming a brightly glowing network of highways within the brain.
It’s exactly what University at Buffalo researcher Shermali Gunawardena was
hoping to see: It meant that ORMOSIL, a novel class of nanoparticles, had
successfully penetrated the insects’ brains. And even after long-term exposure,
the cells and the flies themselves remained unharmed.
The particles, which are tagged with fluorescent proteins, hold
promise as a potential vehicle for drug delivery.
Each particle is a vessel, containing cavities that scientists
could potentially fill with helpful chemical compounds or gene therapies to
send to different parts of the human body. Gunawardena is particularly
interested in using ORMOSIL—organically modified silica—to target problems
within neurons that may be related to neurodegenerative disorders including
Alzheimer’s disease.
The recent study on fruit flies is a step toward making this
happen, demonstrating that long-term exposure to ORMOSIL, through breathing and
feeding, did not injure the animals.
The research appeared in PLoS
ONE.
“We saw that after feeding these nanoparticles in the fruit
fly larvae, the ORMOSIL was going mainly into the guts and skin. But over time,
in adult flies, you could see it in the brain. These results are really
fascinating because these particles do not show any toxic effects on the whole
organism or the neuronal cells,” said Gunawardena, an assistant professor
of biological sciences and a researcher in UB’s Institute for Lasers, Photonics,
and Biophotonics.
The ORMOSIL particles she is investigating are a unique variety
crafted by a research group led by Paras N. Prasad, the UB institute’s
executive director. Each particle contains cavities that can hold drugs, which
can be released when the particles are exposed to light.
Besides Gunawardena and Prasad, co-authors on the study include
Farda Barandeh, Phuong-Lan Nguyen, Rajiv Kumar, Gary J. Iacobucci, Michelle L.
Kuznicki, Andrew Kosterman, and Earl J. Bergey, all from UB.
Gunawardena is an expert in axonal transport. This involves the
movement of motor proteins along neurons’ thread-like axon. These molecular
motors, called kinesins and dyneins, carry “cargo” including vital
proteins to and from the synapse and cell body of neurons.
In this neuronal highway system, one problem that can occur is
an axonal blockage, which resembles a traffic jam in neurons. Proteins
aggregate in a clump along the axon.
Researchers don’t know whether these obstructions contribute to
disorders such as Alzheimer’s or Parkinson’s diseases, which are characterized
by unusual build-ups of proteins called amyloids and Lewy bodies.
But the amyloid precursor protein involved in Alzheimer’s
disease has been shown to have a role in axonal transport, and if axonal
obstructions do turn out to be an early indicator for neurodegeneration seen in
Alzheimer’s disease, eliminating blockages could help prevent or delay the
onset of disease.
That’s where ORMOSIL comes in: Gunawardena hopes to use these
nanoparticles to target drugs to protein jams along axons, breaking up the
accumulations.
Success, if possible, is still a long way off. But the potential
benefit is great. Gunawardena calls the research a “high-risk, high-rewards”
endeavor.
The next step is for her team to see if they can find a way to
force the ORMOSIL to latch onto motor proteins. (The nanoparticles, on their
own, do not move along axons.)
