Fullerene-based low toxic nanocationite particles (porphyrin adducts of cyclohexyl fullerene-C60) to treat hypoxia-induced mitochondrial dysfunction in mammalian heart muscle

Background. This is the first report on the targeted delivery of fullerene-based low toxic nanocationite particles (porphyrin adducts of cyclohexyl fullerene-C-60) to treat hypoxiainduced mitochondrial dysfunction in mammalian heart muscle. Methods. The magnetic isotope effect generated by the release of paramagnetic Mg-25(2+) from these nanoparticles selectively stimulates the ATP overproduction in the oxygen-depleted cell. Results. Because nanoparticles are membranotropic cationites, they will only release the overactivating paramagnetic cations in response to hypoxia-induced acidic shift. The resulting changes in the heart cell energy metabolism result in similar to 80% recovery of the affected myocardium in < 24 h after a single injection (0.03-0.1 LD50). Conclusions. Pharmacokinetics and pharmacodynamics of the nanoparticles suggest their suitability for safe and efficient administration in either single or multi-injection (acute or chronic) therapeutic schemes for the prevention and treatment of clinical conditions involving myocardial hypoxia. (c) 2008 IMSS. Published by Elsevier Inc.