Impact of Fe3O4 nanoparticles in vitro on the contractile activity of smooth muscles of rat antrum and aorta

Background. Magnetic iron oxide nanoparticles are among the most promising materials for creating new theranostics tools for malignant neoplasms. Currently, a number of medical preparations based on iron oxide nanoparticles have been introduced into diagnostic and medical practice, MRI diagnostics, and photosensitizing therapy, as well as a source of iron for patients with a deficiency of this element. However, these nanoparticles are not completely neutral with respect to the functions of organs and tissues of the body, in particular the cardiovascular, respiratory, genitourinary, and central nervous systems. The effect of Fe3O4 nanoparticles on the contraction of smooth muscles of the gastrointestinal tract and aorta has not been studied. The purpose of our study was to clarify the features and mechanisms of the in vitro effect of these nanoparticles on the functional activity of the annular smooth muscles of the stomach and preparations of rat aortic rings. Materials and Methods. A suspension of Fe3O4 nanoparticles in water was used. The nanoparticles were characterized by transmission electron microscopy (TEM) and selected area electron diffraction (SAED). The average hydrodynamic diameter of Fe3O4 nanoparticles in suspension upon stabilization with oleic acid (1%), bovine serum albumin (7.5%), and DMSO (1%) was determined by dynamic light scattering. The tenzometric experiments were conducted in the isometric recording mode on isolated preparations of circular smooth muscles of the antrum and rings of the thoracic aorta of rats. In the case of antrum muscles, contractions were induced by application of a high-potassium solution (80 mM), acetylcholine (10-5 M), and nicotine (10-4 M), and in the case of aortic preparations – a high-potassium solution (80 mM) and epinephrine (10-6 M). Contractions were analyzed by mechanokinetic analysis methods. Results. It was determined that under the conditions of using DMSO as a stabilizer, the suspension contained a minimal quantity of aggregates of Fe3O4 nanopartic­les, showing a peak with an average value of 67.2 nm and a width of 75.3 nm (in terms of number), and was quite stable. It was found that the use of Fe3O4 (10-4 mg/mL) in vitro led to the activation of contractions of smooth muscle preparations of the stomach and aorta caused by the application of a high-potassium solution. Also, under the action of Fe3O4, reversible activation of spontaneous contractions of the smooth muscle of the stomach was observed. Mechanokinetic analysis has established that Fe3O4 caused an increase in force, time, and impulse parameters. It was found that under the action of Fe3O4 nanoparticles, epinephrine-activated contractions of aortic rings and nicotine-activated contractions of stomach preparations were significantly reduced. However, Fe3O4 caused a significant increase in acetylcholine-activated contractions of gastric preparations. Conclusions. Fe3O4 nanoparticles modulate spontaneous and induced contractions of the antrum and aortic smooth muscle preparations. The main mechanisms of such modulation likely involve the activation of voltage-gated Ca2+ ion influx into smooth muscle cells and the sorption of epinephrine and nicotine by these nanoparticles.