Changes in stiffness and morphological features of Walker-256 carcinosarcoma loaded with magnetic nanoparticles in response to a stationary magnetic field
Orel V.Е.1, Dynnyk О.B. 2, Syvak L.A.1, Orel V.B.1, Dasyukevich O.J.1, Rykhalskyi О.Yu.1, Galkin О.Yu.3, Dedkov А.G.1, Golovko T.S.1
- 1National Cancer Institute, Kyiv, Ukraine
- 2Institute of Elastography, Kyiv, Ukraine
- 3National Technical University of Ukraine «Igor Sikorsky Kyiv Polytechnic Institute», Kyiv, Ukraine
Summary. This paper aims to investigate changes in mechanical and histological features of Walker-256 carcinosarcoma loaded with magnetic nanoparticles (MNPs) under the influence of a stationary magnetic field (SMF) based on the magneto-mechanical effect. Object and methods. Non-inbred female rats with Walker-256 carcinosarcoma were randomly divided into three groups. Animals in group 1 received no treatment (control). Fe3O4 MNPs of <50 nm diameter (Sigma, Aldrich, USA) were loaded into the tumor during implantation in groups 2 and 3. The rats assigned to group 3 were then exposed to a non-uniform SMF using a dipole applicator with a neodymium magnet (magnetic induction of 134 mT in the center). In order to assess tumor tissue stiffness, we measured the Young’s modulus based on propagation of shear waves with a Soneus P7 ultrasound scanner (Ultrasign, Ukraine). Histological examination of collected tumor specimens followed standard methods using an Olympus BX-41 microscope (Olympus Europe GmbH, Japan). The nonlinear kinetics of tumor growth was assessed by calculating the growth factor. For statistical analyses, two-sided t-test was used when two groups were compared, and One-way Analysis of Variance (ANOVA) was used for comparison of three groups. Results. A significant decrease in Walker-256 carcinosarcoma growth kinetics was only found after MNPs + SMF treatment as compared with the control and MNPs alone. The Young’s modulus measured in the tumor was significantly higher than in the normal tissue. Tumor tissue showed a 1.7-fold increase in the elastic modulus as compared with the normal tissues of the contralateral limb in group 1. Animals in group 2 showed a 1.9- and 2.7-times greater tumor stiffness than the control and MNCs + SMF treatment, respectively. There was a 28% decrease in the Young’s modulus of Walker-256 carcinosarcoma after MNPs + SMF than in the control group. Importantly, tumor stiffness in group 3 had the nearest value to normal tissues in the contralateral limb. Extensive tumor necrosis was predominant over apoptotic changes in animals receiving MNPs + SMF. Conclusions. The application of SMF to influence the mechanical and morphological features of Walker-256 carcinosarcoma loaded with MNPs based on the magneto-mechanical effect caused the lowest value of the Young’s modulus and the growth factor as compared with MNPs alone and control groups. More pronounced tumor necrosis was observed after MNPs + SMF treatment.
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