Nano-delivery systems for photothermal/starvation therapy and enhanced ferroptosis-immunotherapy

Photothermal therapy (PTT) represents a non-invasive therapeutic modality with considerable potential for tumor ablation. However, the complex tumor microenvironment (TME) presents substantial challenges to conventional PTT monotherapy. In this study, we developed a nanomedicine (Fe₃O₄@GOx@PDA) designed to synergistically eradicate tumor cells by integrating PTT with starvation therapy and ferroptosis induction. Glucose oxidase (GOx) catalyzes the oxidation of intratumoral glucose to gluconic acid and hydrogen peroxide (H₂O₂). Simultaneously, the resultant H₂O₂ facilitates intracellular Fenton-like reactions, generating reactive oxygen species (ROS) that trigger lipid peroxidation. Furthermore, Fe²⁺ ions liberated within the TME react with H₂O₂<i>via</i> a Fenton-like reaction to produce abundant ROS. This ROS surge stimulates macrophage polarization towards the M1 phenotype, thereby further suppressing the proliferation and metastatic potential of colorectal cancer (CRC) cells. This multimodal therapeutic strategy, leveraging Fe₃O₄@GOx@PDA, demonstrates potent synergistic antitumor efficacy coupled with favorable biosafety, presenting a promising therapeutic approach for clinical colorectal cancer management.