Abstract
ABSTRACTObjective:To evaluate the potential of magnetic hyperthermia using aminosilane-coated superparamagnetic iron oxide nanoparticles in glioblastoma tumor model.Methods:The aminosilane-coated superparamagnetic iron oxide nanoparticles were analyzed as to their stability in aqueous medium and their heating potential through specific absorption rate, when submitted to magnetic hyperthermia with different frequencies and intensities of alternating magnetic field. In magnetic hyperthermia in vitro assays, the C6 cells cultured and transduced with luciferase were analyzed by bioluminescence in the absence/presence of alternating magnetic field, and also with and without aminosilane-coated superparamagnetic iron oxide nanoparticles. In the in vivo study, the measurement of bioluminescence was performed 21 days after glioblastoma induction with C6 cells in rats. After 24 hours, the aminosilane-coated superparamagnetic iron oxide nanoparticles were implanted in animals, and magnetic hyperthermia was performed for 40 minutes, using the best conditions of frequency and intensity of alternating magnetic field tested in the in vitro study (the highest specific absorption rate value) and verified the difference of bioluminescence before and after magnetic hyperthermia.Results:The aminosilane-coated superparamagnetic iron oxide nanoparticles were stable, and their heating capacity increased along with higher frequency and intensity of alternating magnetic field. The magnetic hyperthermia application with 874kHz and 200 Gauss of alternating magnetic field determined the best value of specific absorption rate (194.917W/g). When these magnetic hyperthermia parameters were used in in vitro and in vivo analysis, resulted in cell death of 52.0% and 32.8%, respectively, detected by bioluminescence.Conclusion:The magnetic hyperthermia was promissing for the therapeutical process of glioblastoma tumors in animal model, using aminosilane-coated superparamagnetic iron oxide nanoparticles, which presented high specific absorption rate.
Highlights
Glioblastoma (GBM) accounts for 47.7% of all malignant brain tumors, and only 5.6% of patients affected survive up to 5 years after diagnosis, as per the statistical report of the Central Brain Tumor Registry of the United States (CBTRUS),(1) with a prognosis that is still guarded
The curves of figure 2A indicate that the SPIONsAmin are polydispersed in the hydrodynamic size, in which the peak of maximal intensity corresponding to the mean HD was 110±5nm, with no significant difference between the measurements (p>0.05) acquired in 24 hours
Heating can be influenced by physiological aspects that are implicit in the calculation of heat transfer (Pennes equation), such as local metabolism, blood perfusion rates, coefficient of heat transfer in the tissues involved, specific mass of the blood, among others.[32,33] In our study, we obtained 32.5% efficiency with a single application of magnetic hyperthermia (MHT), using the lowest mass value of SPIONsAmin (50μg Fe) in comparison with other studies that applied in the range of 0.5 to 3mg Fe in glioma tumors induced in the flank or subcutaneous regions.[13]. Use of high concentrations of iron nanoparticles can cause toxicity to neighboring tissues, as well as affect other organs associated in the biodistribution and elimination of nanoparticles through the liver, kidneys, and spleen.[34]
Summary
Glioblastoma (GBM) accounts for 47.7% of all malignant brain tumors, and only 5.6% of patients affected survive up to 5 years after diagnosis, as per the statistical report of the Central Brain Tumor Registry of the United States (CBTRUS),(1) with a prognosis that is still guarded. There are some aspects that still need to be assessed relative to efficacy of MHT therapy, such as the physical and chemical properties of the nanoparticles, coatings, size, type of magnetic nanoparticle, AMF parameters (frequency and intensity of oscillating field), concentration of nanoparticles, time of application of MHT, as well as few studies using models of intracerebral glioblastoma.[8,13] One of the magnetic nanoparticles that presents with a great potential is SPIONs coated with aminosilane (SPIONsAmin), as they present with a greater value of saturation magnetization (790.93 A/m) and influences the heating capacity, in comparison with SPIONs coated with other materials, for instance, carboxymethyl-dextran (227.13 A/m).(15) Using SPIONsAmin in assays with MHT, Jordan et al,(9) showed that SPIONs enabled the formation of more stable deposits of nanoparticles around the entire tumor, relative to SPIONs coated with dextran. These SPIONsAmin were evaluated and used for clinical einstein (São Paulo). 2019;17(4):
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