(Keynote) Design of Silica-Containing Redox Nanoparticles for High-Performance Nanotherapeutics

Abstract

Reactive oxygen species (ROS) are known to play a variety of roles at many important events in vivo. However, overproduction of ROS causes serious adverse side effects to the living body. Numerous drugs have been developed and applied to reduce overproduced ROS. Some of them had highly efficient, but not pass clinical evaluation. Since most of these antioxidants are low molecular weight (LMW) compounds, it not only eliminates ROS related to diseases but also destroys the redox reactions necessary for the energy production of living bodies. That is, in the mitochondria in normal cells, ATP production by the electron transport chain is carried out, and a large amount of ROS is generated here, but LMW antioxidants nonspecifically get into normal cells and they erase even such important ROS. In order to improve selective antioxidant properties without damage to these normal redox reactions, we designed new polymer antioxidants. This polymer has self-assembling properties in an aqueous medium and gives nanoparticles. We abbreviate these nanoparticles as redox nanoparticles, RNPs. The nitroxide radicals covalently attached as a side chain of the hydrophobic segment in the amphiphilic block copolymer were compartmentalized into the solid core of the nanoparticles. Unlike LMW antioxidants, RNP is extremely poor in vivo toxicity, as RNPs are less likely to be taken up by healthy cells. Since RNPN has pH-sensitive disintegration properties, it disintegrates at pH decreasing tumors and sites of inflammation. It can therefore be used as pH responsive bioimaging and therapy. We have tried RNPs for the treatment of brain / kidney / myocardial ischemia reperfusions, cerebral hemorrhage, cancer chemotherapy, ulcerative colitis, Alzheimer's disease, etc., and confirmed their effectiveness. Based on polymer antioxidants, we have designed various nanoparticle devices such as antioxidant injectable gels. Among them, antioxidant nanoparticles with high adsorption capacity (siRNP) were designed encapsulation nanosilica in siRNP has proven to be useful as peritoneal dialysis and oral DDS due to its high antioxidant capacity and adsorption capacity. This paper summarizes recent applications of siRNP.