Magnetic hyperthermia therapy for the treatment of glioblastoma: a review of the therapy’s history, efficacy and application in humans

Figures & data

Figure 1. MHT in a patient with a malignant brain tumour. (A) Following the delivery of MNPs to the tumour site, the patient’s head is positioned within an AMF generator. (B) Heat is produced (circles) by MNPs (small spheres) mainly through magnetic hysteresis losses. (C) The localised delivery of MNPs (small spheres) via convection-enhanced delivery (CED) results in a high concentration of MNPs in and around the tumour site. (D) The uptake of MNPs (small spheres) by tumour cells (large structures with a dark center) and macrophages (not shown) results in an enhanced cellular response to heat. Adapted from [46].

Table 1. Data comparison of in vitro studies performed to evaluate the application of MHT for the treatment of gliomas.

Study	Tumour Cell Line	Magnetic nanoparticle composition	Iron concentration (mg/ml)	Temperature reached (°C)	Magnetic field frequency (kHz)	Magnetic field intensity (kA/m)	Duration of AMF exposure (min)	Results
Shinkai et al. [96]	T-9	Magnetite cationic liposomes	7.2, 7.5, 10	42.6, 43.9, 44.8	118	30.6	40–60	No viable tumour cells remained
Ito et al. [97]	T-9	Magnetite cationic liposomes	0.1	42.0	118	30.6	30	Tumour cell apoptosis and necrosis
Meenach et al. [98]	M059K	Polyethylene glycol-based magnetic hydrogel nanocomposites	1.58, 1.92, 2.74, 5.32, 7.24, 7.93	60.7, 59.5, 65.7, 66.1, 73.8, 79.6	297	18–25	5	Tumour cell thermo-ablation
Xu et al. [99]	U251	Iron oxide	2, 4, 6, 8	40, 42, 44, 46	200	Not specified	60	Tumour cell apoptosis and necrosis

Table 2. Data comparison of animal studies performed to evaluate the application of MHT for the treatment of gliomas.

Study	Tumour cell line	Animal model	Tumour cells implantation site	Magnetic nanoparticle composition	Iron concentration (mg/ml)	Temperature reached (°C)	Magnetic field frequency (kHz)	Magnetic field intensity (kA/m)	Duration of AMF exposure (min)	Results
Yanase et al. [100]	T-9	F344 rats	Subcutaneously in the left femoral region	Magnetite cationic liposomes	0.2	43	118	30.6	60	Complete glioma cell death
Yanase et al. [101]	T-9	F344 rats	Subcutaneously in the left femoral region	Magnetite cationic liposomes	0.4	43–44	118	30.6	30	Necrotic tumour cells; some animals displayed complete tumour regression
Yanase et al. [102]	T-9	F344 rats	Subcutaneously in the left and right femoral region	Magnetite cationic liposomes	7.5	43–44	118	30.6	30	Some animals displayed complete tumour regression
Shinkai et al. [96]	T-9	F344 rats	Subcutaneously in the left and right femoral region	Magnetite cationic liposomes	7.5	43–44	118	30.6	30	Some animals displayed complete tumour regression
Ito et al. [97]	T-9	F344 rats	Subcutaneously in the left femoral region	Magnetite cationic liposomes	7.5	42	118	30.6	30	Reduced tumour growth in the immunised animal group
Le et al. [103]	U251-SP	Athymic nude mice	Subcutaneously in the femoral region	Magnetite cationic liposomes	5	43	118	30.6	30	Complete tumour growth suppression
Ohno et al. [104]	T-9	F344 rats	Orthotopic	Carboxymethyl-cellulose magnetite	5.8	44.4	88.9	30.6	30	Significant tumour cell death
Rabias et al. [105]	C6	Wistar rats	Subcutaneously in the area anterior to the bregma	Maghemite	20	Not specified	150	11	20	Tumour tissue damage and dissolution
Jordan et al. [54]	RG-2	F344 rats	Orthotopic	Aminosilane-coated nanoparticles	Not specified	45	100	18	40	Necrotic tumour tissue
Xu et al. [99]	U251	Rats	Subcutaneously in right lower limb	Iron oxide	2, 4, 6, 8	Not specified	200	Not specified	60	Reduced tumour growth

Table 3. Data comparison of clinical studies using MHT in patients with GBM.

Study	Number of patients	Magnetic nanoparticle composition	Median injected volume of magnetic fluid (ml)	Iron concentration (mg/ml)	Magnetic field frequency (kHz)	Magnetic field intensity (kA/m)	AMF duration (min) per session	Total number of AMF sessions	Median survival rate (months)
Maier-Hauff et al. [64]	14	Aminosilane coated superparamagnetic iron oxide nanoparticles dispersed in water	3	112	100	2.5–18	60	4–10	14.5
Maier-Hauff et al. [58]	59	Aminosilane coated superparamagnetic iron oxide nanoparticles dispersed in water	4.5	112	100	2.0–15	60	6	23.2
van Landeghem et al. [126]	3	Aminosilane coated superparamagnetic iron oxide nanoparticles dispersed in water	4.5	112	100	2.5–18	60	6	n/a

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