Effect of magnetic fluid hyperthermia on lung cancer nodules in a murine model

Abstract

Abstract. The purpose of the present study was to investigate the therapeutic effect of magnetic fluid hyperthermia (MFH) induced by an alternating magnetic field (AMF) on human carcinoma A549 xenograft in nude mice. An animal model of human lung cancer was established by subcutaneous injection of human lung cancer A549 cells in BALB/c nude mice. The xenograft mice were randomly divided into four groups and each group was treated with an injection of a different concentration of magnetic fluid: control, low-dose (67.5 mg/ml), medium-dose (90.0 mg/ml) and high-dose group (112.5 mg/ml), respectively. Following the injection (24 h), the tumor was heated in an AMF for 30 min. Tumor volumes were then measured every week. The therapeutic effect was assessed by measuring the tumor volume and weight. Pathological examination was performed with a light and electronic microscope following treatment. The temperature at the surface of the tumor in the low-, medium-and high-dose groups increased to 41.3, 44.5 and 46.8˚C, respectively. The tumor grew significantly slower in the medium-and high-dose groups (both p<0.05) compared to the control group. Cytoclasis and apoptosis were detected under light and electron microscopy. In conclusion, MFH induced by AMF inhibited tumor growth and promoted apoptosis of human carcinoma A549 cells in a xenograft mice model. IntroductionLung cancer is one of the most common malignant tumors worldwide, and its incidence has increased in recent years. Current therapeutic options remain unsatisfactory for most patients. Surgical resection has been identified as the most effective method for the treatment of lung cancer, but it is only available for a small number of patients (1). Therefore, it is crucial to identify a new treatment method.Magnetic fluid hyperthermia (MFH) is a thermal therapy using nanotechnology and hyperthermia, first reported by Jordan et al (2). These authors directly injected magnetic fluids into tumors and increased the temperature using an AMF through the Neel relaxation mechanism (3). Since the magnetic particles were directly injected into tumors, there was no distribution of magnetic particles in the periphery of normal tissues and the temperature of these tissues did not increase significantly. Thus, the hyperthermia specifically targeted the tumors. The efficacy of hyperthermia was demonstrated using MFH in animals with several types of tumors, such as B16 mouse melanoma, T-9 rat glioma, SMMC-7721 mouse hepatocarcinoma and BT-474 mouse breast cancer (4-7). This method was found to be effective in inducing the regression of tumors and increasing the lifespan of the animal. As a result, MFH appears to be a promising method for targeting malignant tumors, including lung cancer.The present study investigated the feasibility of MFH for the treatment of lung cancer with a focus on the antitumor effects of hyperthermia. Materials and methods Magnetic fluids and AMF. Magnetic fluids (Anhui JinkeMagnetic Liquid Co., Ltd., Anhui, China) used in the experiment consisted of supe...

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“…This is a significant increase in survival of the hyperthermia groups compared to the control. In another study by Hu et al, A549 xenograft mice were injected with three different doses of iron oxide MNPs, which resulted in varying tumor temperatures of 41.3, 44.5, and 46.8°C [192]. Tumor temperatures from 42–46°C resulted in disruption of the enzymatic system and structure of the tumor, therefore inducing apoptosis.…”

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“…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.…”