Magnetic fluid hyperthermia for bladder cancer: A preclinical dosimetry study

Abstract

Purpose This paper describes a preclinical investigation of the feasibility of thermotherapy treatment of bladder cancer with Magnetic Fluid Hyperthermia (MFH), performed by analyzing the thermal dosimetry of nanoparticle heating in a rat bladder model. Materials and Methods The bladders of twenty-five female rats were instilled with magnetite-based nanoparticles, and hyperthermia was induced using a novel small animal magnetic field applicator (Actium Biosystems, Boulder, CO). We aimed to increase the bladder lumen temperature to 42°C in <10 min and maintain that temperature for 60 min. Temperatures were measured within the bladder lumen and throughout the rat with seven fiberoptic probes (OpSens Technologies, Quebec, Canada). An MRI analysis was used to confirm the effectiveness of the catheterization method to deliver and maintain various nanoparticle volumes within the bladder. Thermal dosimetry measurements recorded the temperature rise of rat tissues for a variety of nanoparticle exposure conditions. Results Thermal dosimetry data demonstrated our ability to raise and control the temperature of rat bladder lumen ≥1°C/min to a steady-state of 42°C with minimal heating of surrounding normal tissues. MRI scans confirmed the homogenous nanoparticle distribution throughout the bladder. Conclusion These data demonstrate that our MFH system with magnetite-based nanoparticles provide well-localized heating of rat bladder lumen with effective control of temperature in the bladder and minimal heating of surrounding tissues.

Inhibition of heat-shock protein 90 sensitizes liver cancer stem-like cells to magnetic hyperthermia and enhances anti-tumor effect on hepatocellular carcinoma-burdened nude mice

“…[1][2][3] However, the emergence of thermoresistance in tumor cells upon subsequent heating could prevent apoptosis and result in fewer dead cells. 4,5 Heat-shock proteins (HSPs) are associated with thermoresistance and the induction of the heat-shock response, in particular, the up-regulation of HSP90, can impact upon the effect and duration of thermoresistance.…”

Overview of bladder heating technology: matching capabilities with clinical requirements

“…As demonstrated in preclinical studies, the MNP can produce sufficient heating to raise the temperature of the chemotherapeutic mixture in bladder to the desired treatment temperature. (58) Inductively coupled heating is distributed throughout the MNP solution producing relatively homogeneous internal bladder temperature, and convection current mixing of bladder contents further minimizes temperature gradients during treatment. For magnetic coupled nanoparticle solutions, temperature must be monitored with a probe inserted into the bladder through the Foley catheter.…”

“…Rodent studies are most common though larger animals are also used to model the human treatment situation more closely. Since human bladder capacity is approximately 500 ml,(62) the small size of bladder in mice (~ 0.15 ml) and rats (~ 1 – 1.5 ml) requires different heating systems(58, 63). Farm pigs are also used for preclinical studies, with bladder volumes ranging from 250 ml to larger than human bladders.…”

Peptide Conjugated Magnetic Nanoparticles for Magnetically Mediated Energy Delivery to Lung Cancer Cells

“…MMH targets a bulk temperature rise between 42 and 45°C, which can lead to adverse cellular effects, and although MMH has been extensively studied, its translation into the clinic has been limited. MMH studies completed in vitro utilize high bulk nanoparticle concentrations (on the order of mg/ml) to achieve hyperthermia conditions in m onolayer cells or cell suspensions [2,[7][8][9][10], and most in vivo experiments directly inject nanoparticles into tumors (usually subcutaneous) due to the need for high local concentrations to generate a bulk temperature rise [11,12]. Since direct injection is not suitable for many tumors and metastases, there is a gap between bench scale MMH studies and clinical relevance.…”