Acute toxicity and tissue deposition of graphene oxide decorated with platinum nanoparticles following intraperitoneal administration in rats

Abstract

Recently developed novel graphene oxide decorated with platinum nanoparticles (GO/PtNPs) has been recognized for its anticancer properties. Therefore, in vivo studies assessing the toxicity and tissue deposition of these particles are needed. Using a fixed-dose acute toxicity design, rats received a single intraperitonealdose of 300 mg/kg and 2000 mg/kg. After 14 days, the rats were euthanized and analyzed both grossly and microscopically. All rats survived the study, showed no abnormal clinical or behavioral symptoms, and gained body weight normally (22–30 g). GO/PtNPs accumulation was observed predominantly within the abdominal cavity, especially near the injection site, where disseminated black deposits measuring 1–7 mm were detected. Most GO/PtNPs deposits were located within granulomas, either extracellularly or were phagocytosedby macrophages. Macrophages laden with GO/PtNPs were also identified in various organs including mesenteric lymph nodes, liver, spleen, lungs, and kidneys. Degenerative changes of varying degrees were noted in both cardiac and skeletal muscles. Other observations included hydropic degeneration in the liver, acute tubular necrosis in the kidneys of high-dose animals, and hyperemia accompanied by a cribriform state in the brain. The latter was also associated with hemorrhage and gliosis. Notably, no nanoparticle deposits were identified within the brain tissue or cerebral vessel lumens. These findings suggest that, at doses considerably higher than anticipated therapeutic levels, GO/PtNPs can induce marked tissue deposition and selected organ toxicities. Therefore, further studies using therapeutically relevant doses and route-specific experimental designs are required before any medical application of GO/PtNPs can be considered.