Design and application of redox polymers for nanomedicine

Abstract

Reactive oxygen species (ROS), such as superoxide and hydroxyl radicals, cause oxidative stress that strongly affects aging and various diseases. Although various antioxidants have been developed to eliminate ROS, they cause serious problems by destroying important redox reactions in normal cells. We designed redox polymers with antioxidants covalently bonded to them. These polymers, with a self-assembling property, form nanoparticles in aqueous media (redox nanoparticles; RNPs), suppress uptake into normal cells, accumulate at inflammation sites, and effectively prevent ROS-related diseases. As such, RNPs have been found to be effective in preventing diseases involving ROS, such as myocardial and cerebral ischemia-reperfusion injuries, ulcerative colitis, and cancer. Redox polymers have several other applications. We designed redox injectable gels (RIGs), which transform from flowable solution at ambient temperature to gel at body temperature under the physiological conditions. RIGs can be applied for suppression of local inflammation, such as periodontitis. RIGs can also be used in anti-tissue adhesion sprays applied after physical surgery. Redox polymers can also be used as a surface coating of biodevices to make them blood compatible. This review summarizes the synthesis and application of these redox polymers. Amphiphilic block polymers having nitroxide radicals (TEMPO) self-assemble in water to form nanoparticles. This is a new nanomedicine that avoids the adverse effects of conventional antioxidants, which destroy the intracellular redox environment, and makes it possible to treat various oxidative-stress-related diseases such as cerebral or cardiovascular ischemia-reperfusions, Alzheimer’s disease and cancer. In addition, we have designed a gelation function in these materials and developed them as a material for anti-tissue adhesion agents and periodontal diseases. Additionally, we succeeded in enhancing cultured cell functions using an antioxidant biointerface.