Mild Hyperthermia-Enhanced Enzyme-Mediated Tumor Cell Chemodynamic Therapy

The heterogeneity and diversity of tumors seriously attenuate the curative outcome of single treatment modes. Combined therapy has been demonstrated to be a promising candidate to enhance therapeutic efficacy compared with monotherapy. As an emerging therapeutic strategy, chemodynamic therapy (CDT) has drawn extensive attention in recent years. However, the therapeutic efficiency of CDT is still unsatisfying because the level of intracellular hydrogen peroxide (H₂O₂) restricts the production of hydroxyl radicals (^•OH). In this study, a novel curative strategy which combines glucose oxidase (GOx)-mediated Fe₃O₄-based Fenton reaction and multiwalled carbon nanotube (MWNT)-produced mild hyperthermia enhancer is proposed, achieving a mild hyperthermia-enhanced enzyme-mediated tumor cell CDT. GOx can catalyze the conversion of glucose into gluconic acid and H₂O₂, which can elevate acidity in the tumor microenvironment and boost Fe₃O₄-based Fenton reaction, producing a myriad of ^•OH to induce tumor cell death. Furthermore, by using the theory that a temperature rise expedites the kinetics of a chemical reaction, producing a higher reaction rate and more resultants per unit time, we integrate MWNTs in this therapy system, which generate mild hyperthermia so as to accelerate the Fenton reaction for increasing the productivity of ^•OH. Therefore, an amplified CDT can be realized. The therapy platform, mild hyperthermia-enhanced GOx-mediated CDT, provides an effective treatment for cancer and takes CDT a step further.