Second Near‐Infrared Activatable Nitric Oxide Releasing Nanoactuators for Photothermal Combinational Modulation of Epileptogenic Focus

Laser interstitial thermal therapy (LITT), which ablates diseased brain tissues via hyperthermia, has offered novel treatment approach for epilepsy; however, the current LITT protocols still lack ablation selectivity and disease‐modifying efficacy. A second near‐infrared (NIR‐II) activatable nitric oxide (NO) releasing nanoactuator is reported here for photothermal combinational modulation of epileptogenic focus. The nanoactuator is prepared by conjugating NO donor S‐nitrosoglutathione (GSNO) onto polydopamine‐coated gold (Au) nanoparticles (NPs), which shows excellent photothermal conversion capability and controlled NO‐releasing property upon illumination in the NIR‐II window. Both in vitro and in vivo study demonstrate that the nanoactuator could exert stronger cell killing effects as compared to its counterpart. Furthermore, the NIR‐II‐activated NO release could inhibit P‐gp expression by regulating NF‐κb pathway, resulting in reprogramming of epileptogenic microenvironment. This study thus offers a novel regulating strategy for the treatment of drug‐resistant epilepsy.