Ferrous Disulfide‐Based Photothermal Nanocatalyst for NIR‐II Mild Hyperthermia‐Enhanced Chemodynamic Therapy of Temporal Lobe Epilepsy

Photothermal therapy (PTT) has been approved clinically to ablate epileptogenic focus, while the clinical application of this approach is still hindered due to its limited selectivity and potential safety concerns related to extreme hyperthermia. Hypothermal PPT (HPTT) is a novel treatment modality employing mild hyperthermia to ablate abnormal cells, which has a distinctive advantage of minimal side effects on healthy tissues. The significantly elevated hydrogen peroxide (H2O2) concentration in the epileptogenic zone provides a suitable microenvironment for selective chemodynamic therapy (CDT), which utilizes the Fenton reaction of H2O2 and iron‐based nanomaterials to generate cytotoxic free radicals. Herein, the authors report proof‐of‐concept evidence that HPTT and CDT can be successfully integrated to ablate epileptogenic focus. A photothermal nanocatalyst ferrous disulfide nanoplatform is prepared for CDT of epilepsy. More importantly, the CDT efficacy is augmented by the second near‐infrared irradiation‐induced hyperthermia, leading to synergistic HPTT and CDT therapy. In vivo studies on pentylenetetrazole kindling epileptic rats show that the frequency and severity of epileptic attacks are remarkably suppressed after ablation of the epileptogenic focus. It is envisioned that this HPTT augmented CDT strategy may serve as a novel strategy for the treatment of focal epilepsy. A photothermal nanocatalyst (FeS2‐PEG) is prepared to evaluate its efficacy for inducing chemodynamic effects as well as photothermal effects under NIR‐II irradiation. By virtue of the nanoplatforms, a novel combinational hypothermal photothermal therapy (HPTT)/chemodynamic therapy (CDT) treatment modality is developed to ablate epileptogenic focus and shows promise for treating drug‐resistant focal epilepsy.