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

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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