Manganese ferrite-based nanoparticles induce ex vivo, but not in vivo, cardiovascular effects

Allancer DC Nunes,1 Laylla S Ramalho,2 Álvaro PS Souza,1 Elizabeth P Mendes,1,3 Diego B Colugnati,1 Nícholas Zufelato,2 Marcelo H Sousa,4 Andris F Bakuzis,2 Carlos H Castro1,3 1Department of Physiological Sciences, 2Physics Institute, Federal University of Goiás, Goiânia, Brazil; 3National Institute of Science and Technology in Nanobiopharmaceutics, Belo Horizonte, Brazil; 4Faculty of Ceilândia, University of Brasília, Brasília-DF, Brazil Abstract: Magnetic nanoparticles (MNPs) have been used for various biomedical applications. Importantly, manganese ferrite-based nanoparticles have useful magnetic resonance imaging characteristics and potential for hyperthermia treatment, but their effects in the cardiovascular system are poorly reported. Thus, the objectives of this study were to determine the cardiovascular effects of three different types of manganese ferrite-based magnetic nanoparticles: citrate-coated (CiMNPs); tripolyphosphate-coated (PhMNPs); and bare magnetic nanoparticles (BaMNPs). The samples were characterized by vibrating sample magnetometer, X-ray diffraction, dynamic light scattering, and transmission electron microscopy. The direct effects of the MNPs on cardiac contractility were evaluated in isolated perfused rat hearts. The CiMNPs, but not PhMNPs and BaMNPs, induced a transient decrease in the left ventricular end-systolic pressure. The PhMNPs and BaMNPs, but not CiMNPs, induced an increase in left ventricular end-diastolic pressure, which resulted in a decrease in a left ventricular end developed pressure. Indeed, PhMNPs and BaMNPs also caused a decrease in the maximal rate of left ventricular pressure rise (+dP/dt) and maximal rate of left ventricular pressure decline (–dP/dt). The three MNPs studied induced an increase in the perfusion pressure of isolated hearts. BaMNPs, but not PhMNPs or CiMNPs, induced a slight vasorelaxant effect in the isolated aortic rings. None of the MNPs were able to change heart rate or arterial blood pressure in conscious rats. In summary, although the MNPs were able to induce effects ex vivo, no significant changes were observed in vivo. Thus, given the proper dosages, these MNPs should be considered for possible therapeutic applications. Keywords: cardiac function, isolated heart, magnetic fluids, magnetic nanoparticles, nanomedicin