NSTI BioNano 2010

Influence of Mechano– and Magnetochemically Synthesized Magnetosensitive Nanocomplex and Spatially Inhomogeneous Electromagnetic Irradiation on Transplanted Animal Tumor

V.E. Orel, A.D. Shevchenko, A.V. Romanov, I.I. Dzyatkovska, M.O. Nikolov, Yu.G. Mel’nik, N.M. Dzyatkovska, I.B. Shchepotin, V.N. Uvarov
National Cancer Institute, UA

Keywords: nanoparticles, tumor, electromagnetic field

Abstract:

Introduction. The problem during use of magnetic nanoparticles for cancer treatment is high thermal gradients [Jordan A., 2009]. An increase of spatially inhomogeneous electromagnetic field (EF) and local physiological hyperthermia with low thermal gradients and without direct temperature measurements increased antitumor effect of doxorubicin (DR) for transplanted DR-resistant Guerin’s carcinoma and accompanied by the change of thermodynamical entropy [Orel V. E., Romanov A.V., 2010]. In this study we are focusing on the study of the effect of mechano– and magnetochemically synthesized magnetosensitive nanocomplex (MNC) and spatially inhomogeneous electromagnetic irradiation (EI) with low thermal gradients on nonlinear dynamics of the growth for Guerin carcinoma. Materials and Methods. Mechano– and/or magnetochemically synthesized MNC from Fe3O4 nanoparticles with KCl (International Center for Electron Beam Technologies of E.O. Paton, Electric Welding Institute, Ukraine) and DR (Pfizer, Italia) was dried by high-precision tribogenerator. Mechanical processing was performed at a frequency 35 Hz, an amplitude of 9 mm for 5 min using mechanical energy of 20 W/g and EI by 40 MHz with an initial power of 100 W. Mean diameter of Fe3O4 nanoparticles was 20–40 nm. The frequency of spatially inhomogeneous EI for animals was 40MHz with an initial power of 100 W. Magnetic moment m had been studied by means of magnetometer “Vibrating Magnetometer 7404 VSM” (Lake Shore Cryotronics, Inc.,USA) in magnetic fields up to H = 13 000 Oe. The animal tumors irradiated locally by inductive coaxial applicators that had spatial inhomogeneity of EF and initiated mild hyperthermia in tumors (37.9 C). Experimental animals were treated by MNC: DR in the dose 1.5 mg/kg, Fe3O4 with KCl in the dose 3 mg/kg, weight percent of KCl was 3%.The treatment was performed three times by drug and EI from 3 day after tumor transplantation every other two days. Permanent magnet with H = 1990 A/m was disposed in tumor area for localization of MNC in tumour. Nonlinear kinetics of tumor volume was evaluated by growth factor  according to autocatalytic equation and the braking ratio [Emanuel, N., 1977]. Rats were housed in 7 groups: group 1 – control (no treatment); group 2 – treatment by DR; group 3 – DR + ÅI; group 4 – treatment by mechanochemically synthesized ÌNC; group 5 – mechano– and magnetochemically synthesized ÌNC; group 6 – mechanochemically synthesized ÌNC + ÅI; group 7 –mechano– and magnetochemically synthesized ÌNC + EI. Result and Discussion. Magnetometry of DR shows that DR is soft magnetic ferromagnetic (saturation of magnetization ms = 0,88 emu/g, coercitivity Hc = 47.74 Oe, field at ms is equal Hs = 1714.3 Oe), mechanochemically activated Fe3O4 is hard magnetic ferromagnetic (ms = 12.37emu/g, Hc = 79.06 Oe, field at ms is equal Hs = 12 000 Oe) and mechano– and magnetochemically synthesized ÌNC is soft magnetic ferromagnetic (ms = 11.78 emu/g, Hc = 45.66 Oe, field at ms is equal Hs = 11.78 Oe). The growth kinetics of animal tumors is shown in table. The growth kinetics for 7 group had minimal response under the influence of mechano– and magnetochemically synthesized ÌNC and EI. The greatest survival rate of animals was in 6 and 7 groups. They survival rate were on 77 % more than for control group animals. Table. The growth kinetics of Guerin carcinoma from 7 to 24 days after transplantation We purpose, that increase of antitumor effect of MNC was result of spin conversion in radical electron pair during mechano– and magnetochemically synthesizing of ÌNC and EI of animal tumor. Conclusion. In the research of animals with Guerin carcinoma was shown, that mechano– and magnetochemically synthesized magnetosensitive nanocomplex on the basis of nanoparticles of Fe3O4, KCl and doxorubicin and spatially inhomogeneous electromagnetic irradiation with low thermal gradients had a greater antitumor effect than conventional DR.
 
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