ISSN 1995-0780, Nanotechnologies in Russia, 2010, Vol. 5, Nos. 11–12, pp. 844–850. © Pleiades Publishing, Ltd., 2010. Original Russian Text © M.M. Galagudza, D.V. Korolev, D.L. Sonin, I.V. Aleksandrov, V.N. Postnov, G.V. Papayan, E.V. Shlyakhto, 2010, published in Rossiiskie nanotekhnologii, 2010, Vol. 5, Nos. 11–12. 844 INTRODUCTION The concept of targeted drug delivery implies the selective accumulation of drugs in pathologically changed tissue after the systemic introduction of a complex “drug carrier” with a minimal effect on intact organs and tissues from the drug [1]. The idea of tar- geted delivery was first suggested by Paul Ehrlich in 1906 when he introduced the notion of a “magic bul- let” oriented only against target cells with no influence on healthy tissue [2]. In contemporary medical prac- tice, most drugs are applied orally or parenterally, which is accompanied by their natural biodistribution and systemic effect on the organism. It is evident that, in focal pathological processes such as tumor growth, inflammation, and ischemia, a local increase in drug concentration in the pathological zone is more attrac- tive from a clinical point of view; it makes it possible to decrease the toxicity of many preparations and simul- taneously achieve a better therapeutic effect. The use of nanoparticles for the transportation of drugs makes it possible to achieve the targeted delivery of the latter in disturbed tissue, as well as increase the stability of many preparations and their salvation in water. Two variants of targeted delivery with the use of nanoparticles are singled out: passive and active trans- fer. Passive transfer was first described in 1986 when the selective accumulation of drug conjugates in the tumor tissues of mice was revealed [3]. This phenom- enon was called “effect of hypermeability and reten- tion.” Thus, passive transfer is based on the preferen- tial exiting of nanoparticles in the damaged area as a result of the increased meability of vessels of the tumor microvasculature. Active transfer implies the attach- ment of so-called directing ligands to the surface of transport nanoparticles, which provides a highly spe- cific connection of nanoparticles to the damage marker on the target cells. Monoclonal antibodies and their antigen-recognition enzymes, aptamers, and low-molecular compounds (folic acid, for example) are most often used as directing ligands. A typical nan- otransporter for the targeted delivery of drugs consists of several functional elements, namely, a carrier nano- particle with an immobilized drug that directs the ligand in the case of an active transfer and a radioactive or fluorescent label that makes it possible to the assess the biodistribution of nanoparticles in the organism. Until now, studies of the targeted delivery of drugs were mainly concentrated in oncology. However, it could be supposed that the concept of targeted drug delivery may be effectively applied in all local patho- logical processes, including ischemic reperfusion and inflammation. Ischemic heart disease is presently the main cause of death in the world, and it is predicted the situation will not change until 2020 [4]. This is why decreasing the after effects of the ischemic reperfusion of myocardium is one the most important tasks of con- temporary medical science. The targeted delivery of cardioprotective drugs (angiogenic growth factors, recombinant erythropoietin, activators of ATP-sensi- tive potassium channels, etc.) able to bind with nan- otransporters covalently or noncovalently may be one Passive Targeting of Ischemic Myocardium with the Use of Silica Nanoparticles M. M. Galagudza a, b , D. V. Korolev a, b , D. L. Sonin a, b , I. V. Aleksandrov a , V. N. Postnov a, c , G. V. Papayan a, b , and E. V. Shlyakhto a, b a Almazov Federal Heart, Blood and Endocrinology Center, St. Petersburg, ul. Akkuratova 2, 197341 b Pavlov State Medical University, St. Petersburg, ul. L’va Tolstogo 6/8, 197022 c Faculty of Chemistry, St. Petersburg State University, St. Petersburg, Universitetskaya nab. 7–9, 199034 e-mail: galagoudza@mail.ru Received June 13, 2010 Abstract—The clinical outcome in patients with ischemic heart disease can be significantly improved with the implementation of targeted drug delivery directly into the ischemic myocardium. In this study we describe the concept of heart-targeted drug delivery with the use of silica nannocarriers. The techniques of nanopar- ticle functionalization, as well as the data on the effects that silica nanoparticle formulations have on the parameters of systemic hemodynamics, are also presented. The natural biodistribution of fluorescein- and indocyanine green-labeled silica nanoparticles was studied with the use of optical fluorescence. We showed in the study that silica nanoparticles accumulated in the ischemic-reperfused area of the heart, thus providing the first experimental evidence for passive heart targeting. In conclusion, silica nanoparticles are prospective drug carriers that have no toxic effect during acute intravenous administration. DOI: 10.1134/S1995078010110145 ARTICLES