Iron-based theranostic nanoenzyme for combined tumor magneto-photo thermotherapy and starvation therapy

Abstract

To address the issue of high-dose treatment agents in magnetic hyperthermia-mediated multi-model tumor therapy, a unique iron-based theranostic nanoenzyme with excellent magnetothermal and catalytic properties was constructed. By using a high-temperature arc method, the iron carbon nanoparticles (MF1-3) with a particle size between 13.7 and 27.6 nm and shell thickness between 1 and 5 nm were prepared. After screening, we selected MF3 as the magnetic core due to its high Ms. value and excellent thermal properties. Under the magneto-photo dual thermal conditions, MF3 exhibited a remarkable specific absorption rate (SAR) of 4917 W/g, which was 20 times more than that of iron oxide. Notably, MF3 also exhibited best peroxidase (POD)-like catalytic in pH 5.0 and maintained stable catalytic performance at 45 °C. Considering the “starvation” strategy of cutting off the energy supply to tumor cells and killing them, the glucose oxidase (GOX) and chitosan oligosaccharide (COS) was further grafted onto MF3, forming the MF3/GOX/COS. This multifunctional therapeutic nanoenzyme not only exhibited significant peroxidase-like activity, but also had glucose decomposition and glutathione (GSH) consumption capabilities. The thermal effect significantly promoted the uptake of MF3/GOX/COS by 4T1 cells, and the IC50 value of MF3/GOX/COS reached low to 3.75 μg/mL. In vivo anti-tumor experiment, compared with single treatment methods, the combined therapy of MF3/GOX/COS mediated magneto-photo thermotherapy (M-PTT) and starvation therapy (ST) exhibited higher tumor inhibition rate of 82.1 % by increased cell apoptosis through the mitochondrial pathway. Overall, MF3/GOX/COS therapeutic nanoenzyme combined the advantages of nano-catalysis, M-PTT and ST, providing a solution for achieving sustained, stable, and effective tumor inhibition rates at lower dose levels.