Sonodynamic cancer therapy by a nickel ferrite/carbon nanocomposite on melanoma tumor: In vitro and in vivo studies.

Abstract

Reactive oxygen species (ROS)-mediated cancer therapy using light or ultrasound (US) has been widely approached as a non-invasive and inspiring alternative treatment. Sonodynamic therapy (SDT), a non-invasive therapeutic modality of cancer, is an outcome of low-intensity US effect on cancer cells using a sonosensitizer, which results in heat and ROS production followed by cell death. The aim of this study was synthesis, characterization and cancer SDT application of a nickel ferrite/carbon nanocomposite (NiFe2O4/C), as a sonosensitizer. SDT was carried out by applying a 1.0-MHz US radiation at 1.0 W cm-2 of power density and 100% pulse ratio for 60 s. A significant C540 (B16/F10) cell killing was observed in vitro due to ROS production of 100 μg mL-1 of NiFe2O4/C upon SDT. In addition, SDT of melanoma cancer in a mouse model using intratumorally injected NiFe2O4/C of 100 μg mL-1 produced remarkable efficacious recovery in the tumor and significant necrosis (up to 60%) in histological assessments, while injection of NiFe2O4/C or US irradiation alone induced no healing effect. Therefore, SDT using NiFe2O4/C attained success in destroying melanoma cancer and can be developed and introduced as an alternative treatment strategy for melanoma cancer. In furtherance of SDT, magnetic resonance (MR) imaging (1.5 T) in an agarose phantom indicated the effectiveness of NiFe2O4/C as a negative contrast agent in transverse relaxation time-weighted imaging with a corresponding relaxation rate (r2) of 78.9 mmol L-1 s-1. The results confirmed the applicability of the nanocomposite as a theranostics agent for simultaneous SDT and MR imaging.