Magnetic hyperthermia therapy in glioblastoma tumor on-a-Chip model

Abstract

Objective: To evaluate the magnetic hyperthermia therapy in glioblastoma tumor-on-a-Chip model using a microfluidics device. Methods: The magnetic nanoparticles coated with aminosilane were used for the therapy of magnetic hyperthermia, being evaluated the specific absorption rate of the magnetic nanoparticles at 300 Gauss and 305kHz. A preculture of C6 cells was performed before the 3D cells culture on the chip. The process of magnetic hyperthermia on the Chip was performed after administration of 20µL of magnetic nanoparticles (10mgFe/mL) using the parameters that generated the specific absorption rate value. The efficacy of magnetic hyperthermia therapy was evaluated by using the cell viability test through the following fluorescence staining: calcein acetoxymethyl ester (492/513nm), for live cells, and ethidium homodimer-1 (526/619nm) for dead cells dyes. Results: Magnetic nanoparticles when submitted to the alternating magnetic field (300 Gauss and 305kHz) produced a mean value of the specific absorption rate of 115.4±6.0W/g. The 3D culture of C6 cells evaluated by light field microscopy imaging showed the proliferation and morphology of the cells prior to the application of magnetic hyperthermia therapy. Fluorescence images showed decreased viability of cultured cells in organ-on-a-Chip by 20% and 100% after 10 and 30 minutes of the magnetic hyperthermia therapy application respectively. Conclusion: The study showed that the therapeutic process of magnetic hyperthermia in the glioblastoma on-achip model was effective to produce the total cell lise after 30 minutes of therapy.

Magnetic Hyperthermia for Cancer Treatment: Main Parameters Affecting the Outcome of In Vitro and In Vivo Studies

“…The reached temperature was not reported and the contribution of heat for the observed outcome was not excluded, but the authors suggest it to derive from mechanical deterioration. Very recently, Mamica et al proposed a new in vitro model consisting of a tumor-on-a-chip to study the effects of MHT on treating glioblastoma ( Figure 2 ) [ 15 ]. The tumor was mimicked by using rat glioblastoma cells in 3D configuration in a device integrating microfluidics that guarantees the delivery of nutrients to the tumor.…”

“…The whole chip is then submitted to the AMF. Adapted with permission from Reference [ 15 ]. Copyright 2019 Instituto Israelita de Ensino e Pesquisa Albert Einstein.…”

Evolution of Biochip Technology: A Review from Lab-on-a-Chip to Organ-on-a-Chip

“…Magnetic hyperthermia therapy attracted researchers' attention in cancer therapy due to the generation of local heat to minimize damage to healthy cells nearby and optimize the treatment. Recently, a microfluidic based brain tumor-on-a-chip model was developed by Mimani et al [106] to access the therapeutic effect of magnetic hyperthermia on the chip. A 3D cell culture of glioblastoma has been cultivated in the central zone of the microfluidic channel.…”

“…Then, through an alternating magnetic field, magnetic energy transforms to thermal energy and produce heat. Image reproduced from Reference[106].…”

Engineering Three-Dimensional Tumor Models to Study Glioma Cancer Stem Cells and Tumor Microenvironment

“…The interaction within the perivascular niche has also been studied using this technology, suggesting that glioma CSCs located around the vasculature and presenting with the lowest motility are most probably of the proneural subtype, and those with the highest invasiveness are most probably classified in the mesenchymal subtype; which further supports the role of the tumor niche on intratumor heterogeneity and consequent treatment response (Xiao Y. et al, 2019 ). Studies regarding GBM response to magnetic hyperthermia have been also carried out in a similar way (Mamani et al, 2020 ).…”