Full Disappearance of PC3-Luc Prostate Tumors Mediated by Hyperthermia Under Low Intensity Ultrasound Application in the Presence of Magnetosomes

Abstract

Iron oxide nanoparticles have been proposed for magnetic hyperthermia treatment of tumors. However, efficacy depends on the injection of large amounts of such nanoparticles and the equipment is costly. Here, a new thermal cancer treatment is described, in which a tumor containing a low concentration of nonpyrogenic pure iron oxide nanominerals coated with carboxy-methyl-dextran (M-CMD), corresponding to modified magnetosomes, are exposed to ultrasound. Heating PC3 prostate carcinoma cells between 43 and 46°C using ultrasound in the presence of M-CMD resulted in significant necrotic cell death. Furthermore, deposition of M-CMD containing 3 µg of iron per mm³ of tumor in subcutaneous xenografts of PC3-Luc tumors of 150 mm³ followed by 6 to 10 sessions of ultrasound application (1 W cm⁻², 1 MHz) of 10 min each led to a tumor temperature of 43–46°C per session and to total tumor disappearance without regrowth over 6 months following treatment start. Sequential histological analyses of the tumor tissues revealed partial tumor occupation by M-CMD and an increase in cell death over time. Neither lesions, nor magnetosome accumulation were found in microscopic sections of various internal organs collected from treated mice euthanized 6 months after the beginning of the treatment, indicating that M-CMD may not lead to long-term side effects.