RESUMO
Magnetic nanocomposites (MNC) are promising theranostic platforms with tunable physicochemical properties allowing for remote drug delivery and multimodal imaging. Here, we developed doxorubicin-loaded Fe3O4-Au MNC (DOX-MNC) using electron beam physical vapor deposition (EB-PVD) in combination with magneto-mechanochemical synthesis to assess their antitumor effect on Walker-256 carcinosarcoma under the influence of a constant magnetic (CMF) and electromagnetic field (EMF) by comparing tumor growth kinetics, magnetic resonance imaging (MRI) scans and electron spin resonance (ESR) spectra. Transmission (TEM) and scanning electron microscopy (SEM) confirmed the formation of spherical magnetite nanoparticles with a discontinuous gold coating that did not significantly affect the ferromagnetic properties of MNC, as measured by vibrating-sample magnetometry (VSM). Tumor-bearing animals were divided into the control (no treatment), conventional doxorubicin (DOX), DOX-MNC and DOX-MNC + CMF + EMF groups. DOX-MNC + CMF + EMF resulted in 14% and 16% inhibition of tumor growth kinetics as compared with DOX and DOX-MNC, respectively. MRI visualization showed more substantial tumor necrotic changes after the combined treatment. Quantitative analysis of T2-weighted (T2W) images revealed the lowest value of skewness and a significant increase in tumor intensity in response to DOX-MNC + CMF + EMF as compared with the control (1.4 times), DOX (1.6 times) and DOX-MNC (1.8 times) groups. In addition, the lowest level of nitric oxide determined by ESR was found in DOX-MNC + CMF + EMF tumors, which was close to that of the muscle tissue in the contralateral limb. We propose that the reason for the relationship between the observed changes in MRI and ESR is the hyperfine interaction of nuclear and electron spins in mitochondria, as a source of free radical production. Therefore, these results point to the use of EB-PVD and magneto-mechanochemically synthesized Fe3O4-Au MNC loaded with DOX as a potential candidate for cancer magnetic nanotheranostic applications.
RESUMO
An increase of the intracellular reactive oxygen species (ROS) concentration leads to the development of oxidative stress and, thus, to the damage of cell components. The cause-and-effect relations between these processes have not been fully established yet. The ability of photo excited supramolecular composites containing fullerenes C60 immobilized at nanosilica particles to generate reactive oxygen species (ROS) in cells of two types (rat thymocytes, and transformed cells of ascite Erlich carcinoma, EAC, and leucosis L1210) is demonstrated. The damaging effect of photo excited C60-composites are shown, which appeared to be selective and manifested in transformed cells, but not in thymocytes. It has been shown that after the irradiation of aqueous solutions or cell suspensions in the presence of fullerene C60, the generation of reactive oxygen species is observed. It has been shown that the influence of photo excited fullerene C60 on metabolic processes depends on the composition of C60-containing complex and on the type of the cells. The damaging effects of photo excited fullerene C60-containing composites were demonstrated to be selective. The data presented suggest that the application of fullerene C60-containing composites for the selective activation of ROS-dependent death program in certain types of tumor cells is very promising.