A New Fullerene-Based 25Mg-Exchanging Nanocationite for Correction of Doxorubicin-Induced ATP Depletion in Rat Myocardiocytes

It has been recently found that the magnesium-dependent ATP production is a nuclear spin control process (1). It means that, magnetic isotope effect of 25Mg2+, the only magnetic magnesium isotope (+5/2 nuclear spin, 0.85 Bohr magneton magnetic moment, 10% natural abundance), is an essential element in the magnesium-dependent ATP production processes. Both substrate and oxidative phosphorylation pathways, as Mg2+-dependent processes, might be activated up to 2.5-fold more efficiently by milimolars of 25Mg2+ as compared to non-magnetic 24Mg2+ (0 spin, 78% natural abundance) and 26Mg2+ (0 spin, 11% natural abundance) isotopes (1).Recently, a low toxic (LD50=896 mg/kg, i.v., rats), amphiphilic (430 mg/ml water, pH 7.40), membranotropic and cluster forming 1.8-2.0 nm fullerene-C60 based nanoparticles has been designed for correction of hypoxia-induced ATP depletion (2). This product, possessing marked cationite properties, is an iron containing porphyrin monoadduct of a classical fullerene C60, buckminster-fullerene(C60)-2-(butadiene-1-yl)-tetera(o-γ-aminobutyryl-o-phtalyl)ferroporphyrin. Hereafter, we refer it to Porphylleren-MC16 or, in brief, PMC16 (2).This smart nanocationite with membranotropic properties releases the overactivating cations only in response to the intracellular acidosis (2).Doxorubicin (DXR), a widely used anticancer drug, induces cardiotoxicity by ATP depletion and cellular acidosis (3). Thus, it was decided to use 25Mg-carrying PMC16 nanoparticles (25Mg- PMC16) for correction of DXR-induced ATP depletion in myocardial cells.