Background This is the first report on the targeted delivery of fullerene-based low toxic nanocationite particles (porphyrin adducts of cyclohexyl fullerene-C60) to treat hypoxia-induced mitochondrial dysfunction in mammalian heart muscle. Methods The magnetic isotope effect generated by the release of paramagnetic 25Mg2+ 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 ∼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.