Glucose Oxidase-Loaded MnFe2O4 Nanoparticles for Hyperthermia and Cancer Starvation Therapy

Abstract

Nanoparticle-mediated starvation therapy is a promising therapeutic approach for cancer treatment. Here, we report a novel therapeutic nanosystem (GOx@PEG-MnFe2O4) composed of glucose oxidase (GOx) loaded in polyethylene glycol (PEG) modified manganese ferrite (MnFe2O4) nanoparticles (NPs) for cancer starvation therapy. GOx catalyzes the oxidation of glucose to gluconic acid and hydrogen peroxide (H2O2) by consuming oxygen (O2) in an acidic environment. Meanwhile, NPs can catalyze the oxidation of H2O2 to generate O2, which, in turn, aids in the depletion of glucose and eliminate the hypoxia condition. Phase identification, crystal structure, and size of the NPs confirm the cubic spinel structure with an average crystallite size of 21 nm. NPs exhibit good magnetic susceptibility with a magnetization value of ∼75 emu/g at room temperature. Heating potentiality of the NPs with an obtained specific absorption rate (SAR) of 296 W/g proves the efficacy of NPs to act as a heating agent for cancer hyperthermia, which aid for a synergistic therapy combining magnetic hyperthermia with glucose oxidase-based starvation therapy. Fourier transform infrared spectroscopy and thermogravimetry analysis confirm the successful loading of GOx onto the PEG-MnFe2O4 nanosystem. The nanosystem exhibited ∼82% release of GOx in the cancer cell-mimicking environment in an applied magnetic field which is around 1.8 times higher than that in the normal cell-mimicking environment. In vitro assessment against HeLa and Saos-2 cancer cell lines demonstrated anticancer activity and exhibited reduced hemolysis rates. Furthermore, the in vitro results suggested that the NPs are biocompatible and have potential hyperthermic ability. The designed nanosystem is capable of effectuating the tumoricidal effect via cancer starvation therapy.