386 0007-4888/19/16630386--©-2019--Springer-Science+Business-Media,-LLC Bulletin  of  Experimental  Biology  and  Medicine,  Vol.  166,  No.  3,  January, 2019 BIOTECHNOLOGIES Visualization and Cytotoxicity of Fluorescence-Labeled Dimeric Magnetite-Gold Nanoparticles Conjugated with Prostate- Specifc Membrane Antigen in Mouse Macrophages S. K. Pirutin 1,2 , M. V. Efremova 1,3 , A. I. Yusipovich 1 , V. B. Turovetskii 1 , G. V. Maksimov 1 , A. B. Druzhko 2 , and A. G. Mazhuga 1,3,4 Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 166, No. 9, pp. 362-365, September, 2018 Original article submitted November 9, 2017 We demonstrated the possibility of penetration of magnetite-gold nanoparticles conjugated with prostate-specifc membrane antigen into mouse macrophages. It was found that after 3-h incubation with nanoparticles in a concentration of 15 mg/liter at 37 o C, they were seen in only 13% macrophages. In about 90% cells, the nanoparticles were detected within the cytoplasm. Under these conditions, membrane damage was revealed in 25% cells. These results should be taken into account in further development and application of nanomaterials for diagnostic and therapeutic purposes in oncology. Key Words: magnetite-gold nanoparticles; prostate-specifc membrane antigen; macro- phages; cell membranes 1 M. V. Lomonosov Moscow State University, Moscow; 2 Institute of Theoretical and Experimental Biophysics, Russian Academy of Sci- ences, Pushchino, Moscow Region; 3 National University of Science and Technology MISIS; 4 D. I. Mendeleev University of Chemical Technology of Russia, Moscow, Russia. Address for correspondence: pirutin@yandex.ru. S. K. Pirutin New types of magnetic nanoparticles developed du- ring the last decade are now widely used in cell re- search, engineering, and biomedicine [5]. This requires evaluation of their functional and cytotoxic properties. Much attention is now attracted to studies of gold- containing nanoparticles widely used in biological research for delivering various substances into cells, photodynamic and radiotherapy of tumors [3,6]. These particles also uses for in the diagnosis and treatment of various diseases [7]. In particular, magnetic nanoparticle are consid- ered as contrast agents during magnetic resonance imaging (MRI) [11]. The use of MRI in combination with dimeric magnetite-gold nanoparticles (MGN) se- lectively binding to target organs provides additional opportunities for diagnosing and visualization of tu- mors that are diffcult to detect by traditional methods, e.g. X-ray computed tomography [13]. However, the effectiveness of nanoparticles, depends not only on their specifc binding with the target cells, but also on nonspecifc binding with other cells, especially with macrophages. Many contrast agents for MRI based on magnetite nanoparticle cannot be used in clinical practice due to serious side effects [14]. Preliminary studies [9] have demonstrated that absorption of nanoparticles can cause death of liver cells. We studied the possibility of nonspecifc penetra- tion of fuorescent conjugates of modifed MGN with prostate-specifc membrane antigen (PSMA) devel- oped for specifc binding to human prostate cancer cells [10] (Fig. 1), into peritoneal mouse macrophages and evaluated cytotoxicity of these nanoparticles. DOI 10.1007/s10517-019-04356-9