A cerium oxide nanoparticle bound to a human carbonic anhydrase inhibitor (hCAII) has shown promise as a drug-delivery device for treating glaucoma. In a series of experiments, investigators attached hCAII to the nanoparticle and also attached a fluorophore so that they could confirm the attachment and track the particle's inhibitory effects.
Orlando, FL-A specialized cerium oxide nanoparticle developed in a laboratory at the University of Central Florida is a promising drug-delivery device for treating glaucoma. A team of researchers successfully bound a human carbonic anhydrase inhibitor (hCAII) to this nanoparticle and also attached a fluorophore to track the nanoparticle through in vitro and in vivo studies designed to confirm the attachment and test its inhibitory effects.
The enzyme hCAII is believed to play a central role in causing glaucoma. Investigators chose a nontoxic nanoparticle called nanoceria to bind with hCAII to test its potential as an ophthalmic drug-delivery tool, said Sudipta Seal, PhD, an engineering professor with appointments in the Advanced Materials Processing and Analysis Center and the Nanoscience Technology Center at the University of Central Florida in Orlando. Dr. Seal and colleagues from North Dakota University and Duke University carried out their research with support from the National Science Foundation.
"Delivery of the drug to the target is always a challenge, so we decided to functionalize a nanoparticle in such a way that we could put the drug on top of it," Dr. Seal said. "We knew that the nanoparticle would get inside the cell; if that was the case, the attached drug would also get inside the cell."
For the recent study, the researchers chose a carboxybenzenesulfonamide molecule because it has been shown to inhibit carbonic anhydrase and has favorable carboxyl groups for attachment. From previous experiments, they also knew that the nanoparticle was nontoxic.
A carboxyfluorescein molecule was attached so that the team could visualize the cell permeation property of the nanoparticles through a confocal fluorescence microscope. Epichlorohydrin was chosen as the linker molecule.
The functionalization of the nanoceria was confirmed using x-ray photoelectron spectroscopy, while confocal fluorescence microscopy provided further evidence that the fluorescent molecules had bonded. Inhibition studies were performed by mixing the nanoparticles with a solution of 4-nitrophenyl acetate and enzyme and observing the effect on the rate of hCAII-catalyzed hydrolysis. The activity of hCAII declined with increased concentration of nanoceria.
The results of this study were promising, Dr. Seal said, adding that future studies are likely to lead to inhibition of hCAII in living cells and effective treatment of glaucoma and other diseases. An article on these findings was published in the June 28 issue of the Journal of Physical Chemistry C.
Dr. Seal and his collaborator James F. McGinnis, PhD, University of Oklahoma, Norman, are also studying additional nanoceria particles. In a study published last year in Nature Nanotechnology, they showed that nanoceria particles prevent increases in the intracellular concentrations of reactive oxygen intermediates (ROIs) in primary cell cultures of rat retina and, in vivo, prevent loss of vision due to light-induced degeneration of photoreceptor cells. This work could lead to therapies for macular degeneration, retinitis pigmentosa, and other blinding diseases in which ROI-induced cell death is thought to play a role.