Fullerene-based low toxic nanocationite particles (porphyrin adducts of cyclohexyl fullerene-C(60)) 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 hypoxia-induced mitochondrial dysfunction in mammalian heart muscle.


METHODS
The magnetic isotope effect generated by the release of paramagnetic (25)Mg(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 approximately 80% recovery of the affected myocardium in <24 h after a single injection (0.03-0.1 LD(50)).


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.
Amirshahi
Nima
N
School of Pharmacy, I.M. Sechenov Moscow Medical Academy, Moscow, Russian Federation. amirshahi@mail.ru
Alyautdin
Renad N
RN
Sarkar
Saeed
S
Rezayat
Seyed M
SM
Orlova
Marina A
MA
Trushkov
Igor V
IV
Buchachenko
Anatoly L
AL
Kuznetsov
Dmitry A
DA
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D002412:Cations; D037741:Fullerenes / Q000493:pharmacokinetics / Q000633:toxicity*; D006321:Heart / Q000503:physiopathology*; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D018625:Microscopy, Atomic Force; D008929:Mitochondria, Heart / Q000378:metabolism / Q000502:physiology*; D053758:Nanoparticles; D051381:Rats; D017208:Rats, Wistar
D002412:Cations; D037741:Fullerenes; D000255:Adenosine Triphosphate; C069837:fullerene C60