Send cargo to brain in nontoxic ‘vessels’
U. BUFFALO (US) — A novel class of nanoparticles penetrates the brain of fruit flies without harming cells or interfering with normal function, raising the possibility of safe drug delivery, researchers say.
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.
For the new study, published in PLoS One, researchers used ORMOSIL—organically modified silica—to target problems within neurons that may be related to neurodegenerative disorders, including Alzheimer’s disease.
A neuron in primary neuronal cultures generated from the brain of a fruit fly is aglow with ORMOSIL, a nanoparticle that holds potential for delivering drugs to the brain. (Credit: Shermali Gunawardena and PLoS One)
Even after long-term exposure to ORMOSIL through breathing and feeding, fruit flies and their cells remained unharmed.
“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,” says Shermali Gunawardena, assistant professor of biological sciences at the University at Buffalo and a researcher in Buffalo’s Institute for Lasers, Photonics and Biophotonics.
The ORMOSIL particles Gunawardena is investigating are a unique variety crafted by Paras N. Prasad, the institute’s executive director. Each particle contains cavities that can hold drugs, which can be released when the particles are exposed to light.
Gunawardena is an expert in axonal transport that 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.
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.)
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.
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