C60-Serinol to Alleviate the Consequences of Cosmic Radiation

Astronauts on long term space missions incur multiple space radiation risks including cancer, late and early central nervous system effects, cardiovascular diseases, and accelerated aging. A common mechanistic pathway in these events is unchecked oxidative stress. We have developed a countermeasure that protects mice from whole body x-ray radiation-induced death when given systemically 4 hours after lethal radiation exposure. At this time point, a lot of the immediate free radical generation from ionizing radiation exposure has already occurred and yet, we were able to protect these mice. This is largely due to the extremely potent free radical scavenging ability of our C60nbsp;fullerene derivative we term C60-ser that (i) has been made biocompatible by decorating it with a serinol malonamide to dramatically increase its water solubility (gt;250nbsp;mg/ml) and (ii) readily traverses physical barriers within tissues and cells to achieve excellent concentrations in all tissues within the body. C60-ser exists in a dynamic equilibrium state seamlessly flipping between the conjugate monomers (~3nm) and aggregates (100-2000nbsp;nm). Such duality enables the conjugates to use passive diffusion and active transport (e.g. endocytosis, transcytosis) for efficient and seamless shuttling from the vasculature to tissues including the brain. The sub-5nm size also allows a long circulation time by evading opsonization and reticuloendothelial capture and facilitating renal elimination. C60-ser can be reliably and reproducibly created in our facilities by facile and scalable techniques that we have pioneered. The studies proposed in this submission are extensions of this exciting preliminary work that will now explore the ability of C60-ser to protect multiple cell types from charged particle radiotherapy injuries. nbsp;Collectively these studies will set the stage for testing C60-ser in animal models in phase II of this NASA SBIR program.