Medical
Diagnostics | TherapeuticsFree Radicals in Therapeutics
Trapping, Turning & Targeting
A free radical is a molecule with an extra (unpaired) electron. Free radicals seek to pair that electron, in order to become stable, by reacting with another molecule. Free radicals produced within cells can react with membranes, enzymes, and genetic material, damaging or even killing the cell. Free radicals have been implicated in a number of degenerative conditions, from natural aging to Alzheimer's disease.
The transfer of electrons is vital to the chemical processes of life; therefore it is critical to neutralize only pathogenic radicals without blocking vital processes. Fortunately, fullerene nanospheres, unlike most antioxidants, are tunable, which means they can be adjusted to the need. The attachment of different fullerene groups to the outside of the fullerene cage can affect the radical chemistry of the nanosphere. Depending on which groups are attached to the cage, the reactivity of the cage can change. Also, the number of additions to the cage impacts its interaction with radicals.
The transfer of electrons from one species to another is a Redox reaction (short for reduction/oxidation). The species that gains an electron is said to be reduced, while the species that loses an electron is oxidized. Tuned nanospheres act as a Redox buffer. The Redox buffer helps cells manage oxidative stress when pathogenic radicals, like superoxide, overwhelm the natural protective mechanisms. Nanospheres buffer Redox reactions by absorbing pathogenic radicals when they form.
Luna believes another key to success is targeting the radical trap to very specific sites, and is developing novel pharmaceutical products targeted to specific diseases where other antioxidants have been ineffective.
The aqueous compartment within cells includes the cytoplasm, the nucleoplasm and the sites within organelles. The membrane compartments are distinct and of interest because they are sites where electron transfer takes place within mitochondria. Since membranes are two-dimensional liquid crystals, free lipid radicals that partition into the membranes can diffuse laterally quickly, spreading the damage over a wider field.
Chemists in Luna's nanoWorks division have developed a new technology to add to fullerenes that optimize their radical trapping properties while conforming to the rigorous characterization challenges expected for FDA registration. We are testing these candidates and have demonstrated activity in an array of cell culture and animal models of inflammation. These are models where pathogenic radicals play an important role, from arthritis to wound healing. Fullerenes' intrinsic affinity endows them with unique properties that present amazing opportunities as a novel chemotype for designing therapeutics which behave differently from those in use today. We have constructed a compound library which can be used to hit many diverse targets and discover leads based on novel mechanisms.
