Porous Fe₃O₄-GOx theranostic nanoplatform for tumor imaging and starvation/photothermal synergistic therapy.

Cancer remains a global health challenge, calling for integrated strategies that combine precise diagnosis with synergistic treatment. Although glucose oxidase (GOx)-mediated starvation therapy disrupts tumor metabolism by converting glucose into cytotoxic hydrogen peroxide (H2O2), its clinical translation is hindered by inefficient delivery and insufficient monotherapy efficacy. To address these issues, we developed a multifunctional nanoplatform by encapsulating GOx within hollow porous superparamagnetic Fe3O4 nanoparticles (Fe3O4-GOx NPs) to preserve its catalytic activity and enable high loading capacity. This system simultaneously enables magnetic resonance imaging (MRI), photothermal therapy, and enzyme-mediated catalytic intervention. In vitro studies demonstrated strong T2-weighted MRI contrast for precise tumor localization, together with near-infrared laser-triggered hyperthermia that enhance the efficacy of GOx-mediated starvation therapy, elevating oxidative stress and promoting apoptosis in 4T1 cells. In 4T1 tumor-bearing mice, a single administration of Fe3O4-GOx NPs combined with laser irradiation elicited potent tumor suppression through the synergistic effects of intratumoral ROS generation, glucose depletion, and localized photothermal ablation, outperforming either modality alone. Histopathological assessment revealed negligible systemic toxicity and preserved organ integrity. This work presents an integrated theranostic nanoplatform that unites tumor-targeted imaging, enzyme- driven metabolism intervention, and photothermal therapy into a single system, offering a promising strategy for precision cancer management.