Nanomaterials which include nano-sized and nano-structured objects, have gained importance in biomedical research and medicine in recent years. Because of the dramatic increase in surface area when synthesized in the nanometer range, nanomaterials exhibit enhanced or unique reactivity that is not found in their macroscopic counterparts. Many promising nanomaterials are currently under investigation for drug or nucleic acid delivery to target specific organ/tissue for therapy. Others are tested for diagnostic, imaging, tissue healing, and surgical aids . Another unique class of nanomaterials, namely the redox-active radical scavenging nanoparticles including fullerenes and cerium oxide nanoparticles (nanoceria or CeNPs), is being developed as bona fide antioxidants for treatment of neurodegenerative diseases –.
The oxides of cerium, a rare earth element, have unique physical and chemical properties. The cerium ions have both the 3+ and 4+ valence states and therefore can act as electron donors or acceptors. Oxygen defects or vacancies on the surface or subsurface of the lattice crystals act as sites for radical scavenging , . When synthesized in the 3–5 nm range, nanoceria possess enhanced catalytic activities that mimic superoxide dismutase and catalase –, two major anti-oxidative enzymes, to neutralize superoxide anions and hydrogen peroxides, respectively. The enhanced redox capacity of nanoceria is most likely due to the dramatically increased surface to volume ratio of these nanoparticles.
PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH
Dowding, J., Seal, S. and W. T. Self. "Cerium oxide nanoparticles accelerate the decay of peroxynitrite (ONOO-)," , 2013.
Karakoti, A., Singh, S., Dowding, J. M., Seal, S. and W. T. Self. "Redox-active Radical Scavenging Nanomaterials," , v.39, 2010, p. 4422.
Heckert, E., Karakoti, A., Seal, S. and W. T. Self. "The role of cerium redox state in the SOD mimetic activity of nanoceria," , v.29, 2008, p. 2705.
Dowding, J. M., Dosani, T., Kumar, A., Seal, S. and W. T. Self. "Cerium oxide nanoparticles scavenge nitric oxide radical (?NO).," , v.48, 2012, p. 4896.
Babu, S.; Thanneeru, R.; Inerbaev, T.; Day, R.; Masunov, A. E.; Schulte, A.; Seal, S.. "Dopant mediated oxygen vacancy tuning in ceria nanoparticles," , v.20, 2009, p. 085713.
Cai,X., Sezate,S.A., Seal,S. & McGinnis,J.F.. "Sustained protection against photoreceptor degeneration in tubby mice by intravitreal injection of nanoceria," , v.33, 2012, p. 8771.
Singh, S., Kumar, A., Karakoti, A., Seal, S. and W. T. Self. "Unveiling the mechanism of uptake and sub-cellular distribution of cerium oxide nanoparticles.," , v.6, 2010, p. 1813.
Cai,X., Sezate,S.A., Seal,S. & McGinnis,J.F.. "Sustained protection against photoreceptor degeneration in tubby mice by intravitreal injection of nanoceria," , v.33, 2012, p. 8771-8781.
Karakoti, A. S., Monteiro-Riviere, Agarwal, R., Davis, J. P., Narayan, R. J., Self, W. T., McGinnis, J, and S. Seal. "Nanoceria as Antioxidant: Synthesis and Biomedical Applications," , v.33, 2008.
Singh, V., Das, S., Kumar, A., Singh, S., Self, W. T. and S. Seal. "A facile synthesis of PLGA encapsulated cerium oxide nanoparticles: release kinetics and biological activity," , v.4, 2012, p. 2597.
Currently, effective and comprehensive therapies for blinding diseases such as age-related macular degeneration, diabetic retinopathy, and retinitis pigmentosa are still unavailable. Targeting the reduction of reactive oxygen species by nanoceria in these diseased eyes may be one way to prolong the life and function of retinal cells before cures become a reality. Additionally, drug delivery to the posterior segment of the eye, such as the retina, is most effective when administered intravitreally. This procedure, though simple, carries the risk of complications such as infection and retinal detachment, especially when frequent, repeated applications are required. Taken together, nanoceria appear to be ideal candidates as ophthalmic antioxidants because the redox activity of nanoceria is regenerative and frequent repetitive dosing may be avoided. We predict that nanoceria may become the “aspirin” of the 21st century for the therapeutic treatment of eye diseases whose pathologic progression associates tightly with oxidative damage.