Ultrasound-enhanced cascade chemodynamic tumor nanotherapy with lactic acid-enabled hydrogen peroxide self-production

Chemodynamic therapy (CDT) is an effective therapeutic modality for cancer treatment with the action of a catalytic Fenton-like chemoreactive process. To furnish sufficient hydrogen peroxide (H₂O₂) for CDT, catalysts similar to superoxide dismutase are designed to be in cooperation with nanoplatforms. In this work, we rationally integrate lactate oxidase (LOD) with ultrasmall superparamagnetic iron oxide nanoparticles (USPION) to achieve high efficiency of the cascade Fenton reaction for efficient tumor therapy. During the sequential reaction, LOD converts lactic acid into H₂O₂ and pyruvate (PA) in situ, and then USPION with peroxidase-like activity generates large amounts of toxic hydroxyl radicals (˙OH) under the action of H₂O₂. Moreover, the reaction effectively utilizes the excess lactic acid of the tumor microenvironment (TME) as a new target of cancer treatment. To further achieve high-performance tumor treatment, ultrasound has been introduced for augmenting this specific chemoreactive tumor therapy, which can affect cancer cells mainly through sonoporation, cavitation, and thermal effect. With the effects of ultrasound irradiation, this work has constructed an efficient oncology treatment system for tumors. Moreover, the presence of USPION is highly desirable for contrast-enhanced T₁-weighted MRI for monitoring the therapeutic process of cancer in real time.