Source: Industry Frontier Date: 2018-09-20
Researchers at the Institute of Nanoparticle Research at the Institute of Basic Science (South Korea’s IBS) have developed a set of nanoparticles for the treatment of Parkinson’s disease. The trial was tested in mice and published as a “hot paper” on Angewandte Chemie, which represents the first biomedical application of nanoparticles to scavenge reactive oxygen byproducts in Parkinson’s disease and provides new clues to therapeutic goals. .
In the future, the system is expected to be used to identify and treat other conditions caused by reactive oxygen species, including cancer, cardiovascular disease, neurodegenerative diseases and sepsis.
Parkinson’s disease is characterized by sudden degeneration and death of neurons, which secrete dopamine in the brain. The accumulation of reactive oxygen species damages neurons by promoting the onset of mitochondrial dysfunction, neuroinflammation and neuronal death.
The brain’s low antioxidant levels and abundant lipids make it more susceptible to the side effects of reactive oxygen species, including free radicals.
Oxidative stress caused by these molecules in the mitochondria, as well as neuroinflammation caused by intracellular and extracellular oxidative stress, is considered to be an important cause of Parkinson’s disease.
So far, there has been no technology to selectively scavenge reactive oxygen species, nor have they differentiated their effects based on their cellular localization. To address these issues, IBS nanoparticle researchers designed three cerium oxide nanoparticles with different sizes and surface properties to selectively remove reactive oxygen species from mitochondria, intracellular and extracellular spaces.
The cerium oxide nanoparticles against the intracellular space have a size of 11 nm which is small enough to enter the cells and has a negative surface charge (ζ-potential: -23 mV) which prevents them from entering the mitochondrial membrane. The cerium oxide nanoparticles targeting oxygen radicals in the mitochondria are modified with triphenylsulfonium (TPP) to have a positive surface charge of +45 mV.
Finally, nanoparticle clusters of hundreds of thousands of 3 nm cerium oxide nanoparticles having a size of 400 nm and a negative surface charge are capable of removing active oxygen species while remaining outside the cell.
The part of the mouse that is passed to the brain in a mouse model, called the striatum, improves the symptoms of typical Parkinson’s disease: neuroinflammation, oxidative stress and decreased levels of tyrosine hydroxylase – this is Parkinson’s disease A sign – produces dopamine precursors and affects mobility.
Attacking oxidative stress and neuroinflammation from three different aspects enables IBS scientists to identify the most critical therapeutic targets. In particular, removal of reactive oxygen species in the extracellular space with cluster-cerium oxide nanoparticles reduces neuroinflammation, but does not show any effect in reducing oxidative stress and maintaining normal levels of tyrosine hydroxylase.
In contrast, mice treated with cerium oxide nanoparticles and TPP-cerium oxide nanoparticles had significantly higher tyrosine hydroxylase levels than the control. The results indicate that reducing oxidative stress in the intracellular and/or mitochondrial compartment is important for the treatment of Parkinson’s disease.
“These experiments have established an important role for intracellular and mitochondrial reactive oxygen species in the progression and treatment of Parkinson’s disease. We hope that the cerium oxide nanoparticle system will be a useful tool for the development of therapeutic drugs for the treatment of oxidative stress disorders, as well as other degenerative properties. Disease,” explains KWON Hyek Jin, the first author of the study.
“This result is not only the first to develop selective removal of reactive oxygen species from intracellular, extracellular and mitochondrial spaces, but also to study the effects of Parkinson’s disease, the cause of the disease and the new medical applications of nanoparticles.” The study’s correspondent HYEON Taeghwan explained.
Ceria nanoparticles act like artificial antioxidants by mimicking the activity of natural antioxidants such as catalase and superoxide dismutase (SOD). The cerium ions on the surface switch between Ce3 + and Ce 4 + in the presence of reactive oxygen species. In the past, the recyclable function of cerium oxide nanoparticles has been used by the same research team in animal models of ischemic stroke and Alzheimer’s disease.