Porphyrin-fullerene nanoparticles for treatment of hypoxic cardiopathies

Abstract

In this study, low-toxic fullerene-based nanocationite particles (adducts of porphyrin with cyclohexyl fullerene C60) designated for targeted delivery of the paramagnetic stable magnesium isotope to heart muscle is reported for the first time; these particles exhibit a sharp clinical effect of 80% recovery from tissue hypoxia in less than 24 h after a single injection (0.03–0.1 LD50). This therapy is based on a novel principle: 25Mg2+ released by nanoparticles due to the magnetic isotopic effect selectively stimulates the additional production of ATP in oxygen-depleted cells. These cationite “smart nanoparticles,” which possess a membranotropic effect, release hyperactivating paramagnetic cations only in response to a metabolic acidic shift. The final positive changes in the energy metabolism of heart muscle cells are capable of helping to prevent and/or treat local hypoxia of heart muscle, and therefore, protect heart muscle from serious damage in a wide variety of clinical cases of hypoxia, including cardiotoxic side effects of doxorubicin and 1-methylnicotineamide. Both the pharmacokinetics and pharmacodynamics of the proposed drug allow safe and efficient administration in single-and multi-injection (acute and chronic) therapeutic schemes.