Abstract 32: Targeting Toxic Effects of Blood in Intracranial Hemorrhage Models With a Novel Nano-antioxidant/Chelator: A Ferroptosis Specific Treatment?

Introduction: An attractive treatment target following intracerebral hemorrhage (ICH) are reactive oxidative stress (ROS) reactions occurring after contact with blood breakdown products, such as hemin and iron. Recent work suggests the ferroptosis cell death pathway predominates after ICH, likely secondary to ROS and free iron consuming key protection pathways. While studies directed at iron with deferoxamine (DEF) are underway, DEF suffers from poor cellular uptake, short shelf life and toxicity. We report a new version of our well tolerated poly(ethylene glycol)-ated carbon nanodrug, PEG-HCCs, previously demonstrated to have enormous antioxidant capacity and beneficial effects in trauma and ischemia (Samuel et al, PNAS 2015), tested here in ICH models. Methods: PEG-NH2 and DEF have a terminal amine that can be covalently attached via an amide linkage to the HCC (Fig 1a) to achieve a loading of 25 DEF molecules per DEF-HCC-PEG. We tested the effectiveness of DEF-HCC-PEG against the consequences of hemin ...