Therapeutic evaluation of magnetic hyperthermia using Fe3O4-aminosilane-coated iron oxide nanoparticles in glioblastoma animal model.

OBJECTIVE: 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.

Therapeutic evaluation of magnetic hyperthermia using Fe3O4-aminosilane-coated iron oxide nanoparticles in glioblastoma animal model / Avaliação terapêutica da técnica de magneto-hipertermia utilizando nanopartículas de Fe3O4 recobertas com aminosilana em modelo animal de glioblastoma

ABSTRACT Objective: 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.

RESUMO Objetivo: Avaliar o potencial da técnica de magneto-hipertermia utilizando nanopartículas superparamagnéticas de óxido de ferro recobertas com aminosilana em modelo de tumores de glioblastoma. Métodos: As nanopartículas superparamagnéticas de óxido de ferro recobertas com aminosilana foram avaliadas quanto à sua estabilidade em meio aquoso e a seu potencial de aquecimento pela taxa de absorção específica, quando submetidas à magneto-hipertermia, com diferentes frequências e intensidades de campo magnético alternado. Nos ensaios de magneto-hipertermia in vitro, as células C6 cultivadas e transduzidas com luciferase foram avaliadas por bioluminescência na presença/ausência do campo magnético alternado, como também com e sem nanopartículas superparamagnéticas de óxido de ferro recobertas com aminosilana. No estudo in vivo, a medida de bioluminescência foi adquirida no 21º dia após indução do glioblastoma com células C6 nos ratos. Após 24 horas, as nanopartículas superparamagnéticas de óxido de ferro recobertas com aminosilana foram implantadas no animal, tendo sido realizada a magneto-hipertermia por 40 minutos, nas melhores condições de frequência e intensidade de campo magnético alternado testado no estudo in vitro (maior valor da taxa de absorção específica); foi verificada a diferença do bioluminescência antes e após a magneto-hipertermia. Resultados: As nanopartículas superparamagnéticas de óxido de ferro recobertas com aminosilana se mostraram estáveis, e sua capacidade de aquecimento aumentou com o incremento da frequência e da intensidade de campo magnético alternado. A aplicação da magneto-hipertermia, com 874kHz e 200 Gauss do campo magnético alternado, determinou o melhor valor da taxa de absorção específica (194,917W/g). Quando utilizados, estes parâmetros de magneto-hipertermia in vitro resultaram em morte celular de 52,0% e in vivo de 32,8% por bioluminescência. Conclusão: A técnica de magneto-hipertermia foi promissora para o processo terapêutico de tumores de glioblastoma no modelo animal utilizando as nanopartículas superparamagnéticas de óxido de ferro recobertas com aminosilana recobertas com aminosilana, que apresentaram alta taxa de absorção específica.

Image and motor behavior for monitoring tumor growth in C6 glioma model.

The primary objective of this study is to monitor tumor growth by using image techniques and behavioral testing through general and specific motor activities (spontaneous movements and gait). Our sample includes male Wistar rats, 2 months old and weighing 250-300 g, that is categorized into three groups: control, sham, and experimental. The experimental group was anesthetized; the C6 cells with luciferase expression that were suspended in a culture medium were implanted into the right frontoparietal cortex of the rats. The sham group received implant only with culture medium without cells. Images and behavioral tests were evaluated at base time and at 7, 14, 21, and 28 days after induced tumor growth analysis. The tumor volume measured by magnetic resonance imaging (MRI) and quantitative bioluminescence imaging (BLI) signal showed a correlation coefficient of r = 0.96. The MRI showed that the mean tumor volume increased by approximately 10, 26, and 49 times according to a comparison of tumor volume on the seventh day with 14, 21, and 28 days, respectively. The quantification of the BLI signal was (4.12 ± 2.01) x 10(8), (8.33 ± 3.12) x 10(8), (28.43 ± 6.32) x 10(8), and (63.02 ± 10.53) x 10(8) photons/s at the seventh, fourteenth, twenty-first, and twenty-eighth day, respectively. After 14 days of tumor induction, both behavioral tests showed significant differences between tumor and sham or control groups. Our study showed a high correlation between MRI and BLI for tumor growth monitoring with complement aspects analysis in tumor volume. In addition, functional behavioral analysis displayed sensitivity to monitor tumor growth, as well as to detect early significant changes between groups, primarily in the tumor group. The results of gait analysis were more sensitive than general motor analysis.