Therapeutic Efficiency of Multiple Applications of Magnetic Hyperthermia Technique in Glioblastoma Using Aminosilane Coated Iron Oxide Nanoparticles: In Vitro and In Vivo Study

Abstract

Magnetic hyperthermia (MHT) has been shown as a promising alternative therapy for glioblastoma (GBM) treatment. This study consists of three parts: The first part evaluates the heating potential of aminosilane-coated superparamagnetic iron oxide nanoparticles (SPIONa). The second and third parts comprise the evaluation of MHT multiple applications in GBM model, either in vitro or in vivo. The obtained heating curves of SPIONa (100 nm, +20 mV) and their specific absorption rates (SAR) stablished the best therapeutic conditions for frequencies (309 kHz and 557 kHz) and magnetic field (300 Gauss), which were stablished based on three in vitro MHT application in C6 GBM cell line. The bioluminescence (BLI) signal decayed in all applications and parameters tested and 309 kHz with 300 Gauss have shown to provide the best therapeutic effect. These parameters were also established for three MHT applications in vivo, in which the decay of BLI signal correlates with reduced tumor and also with decreased tumor glucose uptake assessed by positron emission tomography (PET) images. The behavior assessment showed a slight improvement after each MHT therapy, but after three applications the motor function displayed a relevant and progressive improvement until the latest evaluation. Thus, MHT multiple applications allowed an almost total regression of the GBM tumor in vivo. However, futher evaluations after the therapy acute phase are necessary to follow the evolution or tumor total regression. BLI, positron emission tomography (PET), and spontaneous locomotion evaluation techniques were effective in longitudinally monitoring the therapeutic effects of the MHT technique.

Antiangiogenic Targets for Glioblastoma Therapy from a Pre-Clinical Approach, Using Nanoformulations

“…Therefore, many of the selected studies used human U87-MG tumor cells [ 32 , 34 , 38 , 52 , 53 , 55 , 56 , 57 , 58 , 59 , 62 , 63 , 64 , 66 , 67 ], in which the tumor has a diffusely invasive infiltration pattern into normal brain parenchyma, resistance to therapy, and high recurrence rate [ 70 ]. Studies also used rat C6 tumor cells [ 41 , 51 , 54 , 60 , 61 ], in which the tumor mimics several features of human GBM including a high mitotic index, focal tumor necrosis, parenchymal invasion, and neoangiogenesis [ 71 , 72 ]. The GBM orthotopic model was induced mainly in immunosuppressed animals (e.g., nude or SCID ) because this immunodeficient condition allows a greater possibility of the growth of human (xenogeneic) tumor cells after implantation, preventing their rejection [ 73 ].…”

Utilizing Iron for Targeted Lipid Peroxidation as Anticancer Option of Integrative Biomedicine: A Short Review of Nanosystems Containing Iron

“…Compared to ferromagnetics, superparamagnetic iron oxide nanoparticles generate more heat and are extensively used in cancer therapy. Superparamagnetic properties of iron oxide nanoparticles have shown promising results in the hyperthermia treatment of solid tumors such as prostate cancer [67,68] and glioblastoma [69,70]. Impressively, almost complete glioblastoma regression was observed after multiple applications of magnetic hyperthermia [70].…”

“…Superparamagnetic properties of iron oxide nanoparticles have shown promising results in the hyperthermia treatment of solid tumors such as prostate cancer [67,68] and glioblastoma [69,70]. Impressively, almost complete glioblastoma regression was observed after multiple applications of magnetic hyperthermia [70]. For further reading on the medical applications of SPIONs, a Chemodynamic therapy (CDT) with a high specificity towards a tumor microenvironment (TME) is a promising strategy for the management of cancer.…”

Nanoparticles for Stem Cell Therapy Bioengineering in Glioma

“…Active targeting is achieved by different methods; a method called ligand targeting works by coating the nanoparticles' surface with one or more ligands such as transferrin, epidermal growth factor (EGF), folic acid, arginyl-glycyl-aspartic tripeptide (RGD) peptide, hyaluronic acid, antibodies, and others (Ruiz-Garcia et al, 2020). These ligands allow NPs to bind specific "receptors" differentially expressed only in certain cancerous blood vessels and/or tumor cells, thus leading to a precise cellular internalization (Maier-Hauff et al, 2007;Kim et al, 2010;Wegscheid et al, 2014;Cheng Y. et al, 2016;Shen et al, 2017;Yu et al, 2017Yu et al, , 2019Hua et al, 2018;Daniel et al, 2019;Denora et al, 2019;Dufort et al, 2019;Kefayat et al, 2019;Kunoh et al, 2019;Luque-Michel et al, 2019;Rego et al, 2019Rego et al, , 2020Ruan et al, TABLE 3 | Advances in the uses of nanoparticles in glioma therapy and diagnosis.…”

“…• In vivo: SPIONa (Rego et al, 2019(Rego et al, , 2020Shi et al, 2019) Sonodynamic therapy Preclinical…”