Nephrotoxicity of dextran functionalized graphene nanoparticles and their potential as magnetic resonance imaging contrast agents for renal abnormalities

Contrast-enhanced magnetic resonance angiography (MRA) employs the use of blood pool contrast agents (CA) such as gadolinium (Gd³⁺) complexes that allow for delayed phase arterial and venous imaging and improve the sensitivity in detecting small vascular defects. However, recent association of Gd³⁺-based CA with nephrogenic systemic fibrosis (NSF), a debilitating disease characterized by progressive and severe thickening of the skin, in patients with renal insufficiency has led to restrictions on their clinical use by the FDA. We have developed a dextran functionalized manganese intercalated graphene-based CA with relaxivity values 20X greater than current clinically approved CAs. In this work, we report the safety and efficacy of our novel CA for renal in vivo MRA. The propensity for our contrast agent (at 5 and 50 mg/kg doses) to induce histopathological signs of NSF was evaluated in an experimental rat model of chronic renal failure. In vivo studies indicate that Mangradex formulations are safe and show no nephrotoxic effects after chronic exposure at doses < 50 mg/kg. MR imaging results indicate Mangradex's excellent potential as a blood pool CA.