The porphyrin-fullerene nanoparticles to promote the ATP overproduction in myocardium: 25Mg2+-magnetic isotope effect

被引：40

作者：

Rezayat, S. M. ^{[2
]}

Boushehri, S. V. S. ^{[2
]}

Salmanian, B. ^{[2
]}

Omidvari, A. H. ^{[2
]}

Tarighat, S. ^{[2
]}

Esmaeili, S. ^{[2
]}

Sarkar, S. ^{[3
]}

Amirshahi, N. ^{[1
]}

Alyautdin, R. N. ^{[1
]}

Orlova, M. A. ^{[4
]}

Trushkov, I. V. ^{[4
]}

Buchachenko, A. L. ^{[5
]}

Liu, K. C. ^{[5
]}

Kuznetsov, D. A. ^{[5
]}

机构：

[1] IM Sechenov Moscow Med Acad, Sch Pharm, Moscow, Russia

[2] Univ Tehran Med Sci, Sch Med, Tehran, Iran

[3] Tehran Univ Med Sci, Res Ctr Sci & Technol Med, Tehran, Iran

[4] Moscow MV Lomonosov State Univ, Dept Chem, Moscow, Russia

[5] Russian Acad Sci, NN Semenov Chem Phys Inst, Moscow, Russia

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 44卷 / 04期

关键词：

Porphyrin-fullerenes; Myocardium hypoxia; Mg-25(2+)-magnetic isotope effect; ATP overproduction; WATER-SOLUBLE FULLERENE; SPIN BIOCHEMISTRY; MAGNESIUM; C-60; NANOTECHNOLOGY; STATE;

D O I：

10.1016/j.ejmech.2008.07.030

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

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 LD50). A whole principle of this therapy is novel: Mg-25(2+)-magnetic isotope effect selectively stimulates the ATP overproduction in the oxygen-depleted cells due to Mg-25(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. (C) 2008 Elsevier Masson SAS. All rights reserved.

引用

页码：1554 / 1569

页数：16

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