Redox Buffering Capacity of Nanomaterials as an Index of ROS-Based Therapeutics and Toxicity: A Preclinical Animal Study

Precise control of intracellular redox status, i.e., maintenance of the physiological level of reactive oxygen species (ROS) for mediating normal cellular functions (oxidative eustress) while evading the excess ROS stress (distress), is central to the concept of redox medicine. In this regard, engineered nanoparticles with unique ROS generation, transition, and depletion functions have the potential to be the choice of redox therapeutics. However, it is always challenging to estimate whether ROS-induced intracellular events are beneficial or deleterious to the cell. Here, we propose the concept of redox buffering capacity as a therapeutic index of engineered nanomaterials. As a steady redox state is maintained for normal functioning cells, we hypothesize that the ability of a nanomaterial to preserve this homeostatic condition will dictate its therapeutic efficacy. Additionally, the redox buffering capacity is expected to provide information about the nanoparticle toxicity. Here, using citrate-functionalized trimanganese tetroxide nanoparticles (C-Mn3O4 NPs) as a model nanosystem, we explored its redox buffering capacity in erythrocytes. Furthermore, we went on to study the chronic toxic effect (if any) of this nanomaterial in the animal model to co-relate with the experimentally estimated redox buffering capacity. This study could function as a framework for assessing the capability of a nanomaterial as redox medicine (whether maintains eustress or damages by creating distress), thus orienting its application and safety for clinical use.

Automated summary

Precise control of redox status in cells is crucial for maintaining normal cellular functions, and engineered nanoparticles with unique ROS functions may be potential redox therapeutics. The concept of redox buffering capacity as a therapeutic index for nanomaterials could provide valuable information on therapeutic efficacy and nanoparticle toxicity. This study explores the redox buffering capacity of nanoparticles in red blood cells and their chronic toxic effects in animal models, offering insights into the application and safety of nanomaterials in redox medicine.