Ormosil particles in axons of fruit fly neurons appear as bright red spots. Even after long-term exposure, the cells and the flies themselves remain unharmed. (Credit: Shermali Gunawardena; PLoS One).
Medical researchers and materials scientists have been collaborating in many places to develop novel micro-targeted drug delivery systems, often with multiple functions in mind. For example, an ideal material would be able to serve as “mule” for a therapeutic drug, be tracked in the body and be able to release the drug at times and locations determined by a physician. Materials in the world of ceramic and glass are of keen interest to these researchers because they can be made to be inert and mirror materials already found in humans and animals.
Indeed, various groups are testing drug and imaging systems based on glass microbeads, nanodiamonds and mesoporous silica. Another similar material is Ormosil, or organically modified silica. Each of these can be combined with a variety of fluorophores for imaging and tracking purposes. The pores, cavities and surfaces of these materials permit bioactive molecules such as enzymes, genetic materials and chemotherapeutic drugs to be incorporated into them. So far, in many cases in vitro testing of these has been encouraging and many are slowing working their way towards in vivo applications.
As in vivo testing approaches, the issue of how truly biocompatible these materials are becomes more important. Along these lines, a group out of the University of Buffalo investigating treatments for neurodegenerative disorders has been testing Ormosil nanoparticles in fruit flies, and in a new paper they report that even after long-term exposure to Ormosil, cells harvested from throughout the Drosophila show no harm from the material. Besides biocompatibility, their work also indicates that the “Ormosil nanoparticles penetrate into living brains, neuronal cell bodies and axonal projections. … Strikingly, incorporation of ORMOSIL nanoparticles into the [Drosophila] brain did not induce aberrant neuronal death or interfere with normal neuronal processes.”
One of the UB researchers, Shermali Gunawardena, reports in a news release, “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.”
Gunawardena works alongside Paras N. Prasad in the school’s Institute for Lasers, Photonics and Biophotonics. Prasad, who heads the ILPB, designed the Ormosil particles to have cavities that can be filled with a therapeutic drug that can be released when exposed to a specific light source. Gunawardena’s expertise is diseases that appear to be caused by problems arising in the chemical transportation systems found in neurons, such as the ones responsible for shuttling key proteins. There is evidence of a link to Alzheimer’s or Parkinson’s and other diseases when the transportation system falters and proteins accumulate. She hopes to use these nanoparticles to target drugs to protein jams, breaking up the accumulations.
In their paper published in PLoS ONE (doi:10.1371/journal.pone.0029424), Gunawardena, Prasad et al. are clearly optimistic. They say
“[O]ur study demonstrates that Ormosil nanoparticles have great promise for the development of therapeutic applications for human neuronal disease for long-term use within whole organisms. Its nontoxic characteristic and its ability to readily incorporate into living neuronal tissues together with its porous surface that allows incorporation of specific molecules for targeting, make Ormosil nanoparticles the next generation of particles that can be effectively used to develop targeted therapeutic treatments to specific areas of the brain or to specific populations of neurons. Development of such treatment strategies have great potential in minimizing global deleterious affects while maximizing beneficial affects, which is a problem in many of the current treatment strategies that are used for many human neuronal diseases.”