The porphyrin-fullerene nanoparticles to promote the ATP overproduction in myocardium: 25Mg2+-magnetic isotope effect.
This is a first case ever reported on the fullerene-based low toxic nanocationite particles (porphyrin adducts of cyclohexyl fullerene-C(60)) designed for targeted delivery of the paramagnetic magnesium stable isotope to the heart muscle providing a sharp clinical effect close to about 80% recovery of the tissue hypoxia symptoms in less than 24 h after a single injection (0.03-0.1 LD(50)). A whole principle of this therapy is novel: (25)Mg(2+)-magnetic isotope effect selectively stimulates the ATP overproduction in the oxygen-depleted cells due to (25)Mg(2+) released by the nanoparticles. Being membranotropic cationites, these "smart nanoparticles" release the overactivating paramagnetic cations only in response to the metabolic acidic shift. The resulting positive changes in the heart cell energy metabolism may help to prevent and/or treat the local myocardial hypoxic disorders and, hence, protect the heart muscle from a serious damage in a vast variety of the hypoxia-caused clinical situations including both doxorubicin and 1-methylnicotineamide cardiotoxic side effects. Both pharmacokinetics and pharmacodynamics of the drug proposed make it suitable for safe and efficient administration in either single or multi-injection (acute or chronic) therapeutic schemes.
Rezayat
S M
SM
School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. rezayat@sina.tums.ac.ir
Boushehri
S V S
SV
Salmanian
B
B
Omidvari
A H
AH
Tarighat
S
S
Esmaeili
S
S
Sarkar
S
S
Amirshahi
N
N
Alyautdin
R N
RN
Orlova
M A
MA
Trushkov
I V
IV
Buchachenko
A L
AL
Liu
K C
KC
Kuznetsov
D A
DA
D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D055808:Drug Discovery; D037741:Fullerenes / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000139:chemically induced / Q000378:metabolism; D007554:Isotopes / Q000737:chemistry; D008274:Magnesium / Q000737:chemistry* / Q000378:metabolism; D008280:Magnetics; D008297:Male; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D053758:Nanoparticles / Q000737:chemistry*; D033363:Neutron Diffraction; D010100:Oxygen / Q000378:metabolism; D011166:Porphyrins / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D053838:Scattering, Small Angle
D037741:Fullerenes; D007554:Isotopes; D011166:Porphyrins; D000255:Adenosine Triphosphate; D008274:Magnesium; C069837:fullerene C60; D010100:Oxygen