Medium Temperature Independent Cytotoxicity of Cell-adhesive Heat-generating Nanoparticles Named Magnetite Cationic Liposomes and its Therapeutic Use

Abstract

Cancer clinical research using heat-generating nanoparticles named magnetite cationic liposomes (MCL) has been conducted. Heat generation from intratumorally injected MCL particles was induced by alternating magnetic field (AMF) irradiation to kill cancer cells nearby located. Its feasibility and safety have been shown but efficacy was variable among tumors whose temperature rises were similarly achieved. To ensure efficacy heat dose divided by tumor volume (J/cm3) has been proposed as candidate index to control clinical treatment. Purpose of this study is to investigate cytotoxicity of MCL particles upon AMF irradiation and discuss validity of the proposed index. MCL particles were shown to adsorb human prostate cancer cells in vitro at 2 ng-MCL/cell, depending on positive zeta potential derived from a cationic lipid component. Optical and electron microscopic observations showed majority of MCL particles located on cell membrane and scarcely in cytosol. Heat generation activities of MCL particles were represented by specific absorption rate (SAR) with unit of J/g-MCL・min and were shown variable due to irradiation conditions. Cytotoxicity of MCL particles upon AMF irradiation was found under a condition supplying heat dose of 1.2×10-4 J/cell with concomitant cellular morphological changes and membrane burst. Notably, temperature rise of culture medium was not observed under this condition. Cytotoxicity of MCL particles was considered to be caused by heat generated locally on cell membrane (J/cell) independently of medium temperature. These results would support the proposed heat dose index (J/cm3 tumor volume) to control clinical treatment instead of tumor temperature.