Abstract
Cobalt manganese ferrite nanoparticles have application potential in the biomedical field, however there is limited information concerning the biological response. The aim of this work was to investigate the cytotoxic potential of cobalt-manganese ferrite nanoparticles in canine mastocytoma tumor cells (C2) and adipose-derived mesenchymal stromal stem cells (ASCs) cultured under a static magnetic field (MF). In this study, we investigated the viability and proliferation rate of ASC and C2 cells cultured with Co0.2Mn0.8Fe2O4 nanoparticles under 0.5T MF. We observed cells morphology and measured intracellular ROS generation. Thermal observations were used to characterize the thermotrophic cell behavior in different condition and RNA level of heat shock proteins and apoptotic genes was measured. Nanoparticles reduced cell viability, caused cell damage, i.e., through the formation of reactive oxygen species (ROS) and increased transcriptional level of apoptotic genes (Bcl-2, Bax, p53, p21). In addition, we have found that C2 mastocytoma cells cultured with metal oxide nanoparticles under MF exhibited unexpected biological responses, including thermotolerance and apoptotic response induced by the expression of heat shock proteins and ROS produced under a MF. Our results suggest that stimulation using MF and Co0.2Mn0.8Fe2O4 nanoparticles is involved in mechanisms associated with controlling cell proliferative potential signaling events. We can state that significant differences between normal and cancer cells in response to nanoparticles and MF are apparent. Our results show that nanoparticles and MF elevate the temperature in vitro in tumor cells, thereby increasing the expression of ROS as well as heat shock proteins.
Highlights
Mast cell tumors (MCTs) are the most common skin malignancy in dogs, comprising 16–21% of all cutaneous tumors diagnosed,[33,37] mainly originating from neoplastic transformation of resident tissue mast cells or their progenitors.[34]Canine MCTs demonstrate varying physiological behaviors, ranging from solitary benign masses, which can be cured with surgery alone, to a systemic and potentially fatal metastatic disease.[38,56] In contrast to normal tissue, MCT microenvironment often lacks oxygen, is acidic and contains high levels of reactive oxygen species (ROS)
To determine whether magnetic nanoparticles (MNPs) and magnetic field (MF) treatment could affect the level of oxidative stress factors, we evaluated the level of ROS after 72 h of culture (Fig. 5b)
Our results suggest that cobalt-manganese ferrite nanoparticles are potentially an effective tool for hyperthermic treatment of dog skin mastocytoma
Summary
Mast cell tumors (MCTs) are the most common skin malignancy in dogs, comprising 16–21% of all cutaneous tumors diagnosed,[33,37] mainly originating from neoplastic transformation of resident tissue mast cells or their progenitors.[34]Canine MCTs demonstrate varying physiological behaviors, ranging from solitary benign masses, which can be cured with surgery alone, to a systemic and potentially fatal metastatic disease.[38,56] In contrast to normal tissue, MCT microenvironment often lacks oxygen (hypoxia), is acidic (acidosis) and contains high levels of reactive oxygen species (ROS). Canine MCTs demonstrate varying physiological behaviors, ranging from solitary benign masses, which can be cured with surgery alone, to a systemic and potentially fatal metastatic disease.[38,56]. In contrast to normal tissue, MCT microenvironment often lacks oxygen (hypoxia), is acidic (acidosis) and contains high levels of reactive oxygen species (ROS). Together, these factors promote tumor growth, spread and resistance to cancer therapies, leading to treatment failures. Dogs with a localized MCT are often cured by local therapy (surgery and/or radiation therapy), those with an inoperable primary mass or confirmed disseminated disease usually die.[4,56]
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