A Sonoresponsive and NIR-II-Photoresponsive Nanozyme for Heterojunction-Enhanced "Three-in-One" Multimodal Oncotherapy.

Albeit low-cost nanozymes with excellent stability have demonstrated the potential to be highly beneficial for nanocatalytic therapy (NCT), their unsatisfactory catalytic activity accompanied by intricate tumor microenvironment (TME) significantly hinders the therapeutic effect of NCT. Herein, we report, for the first time, a heterojunction (HJ)-fabricated sonoresponsive and NIR-II-photoresponsive nanozyme by assembling carbon dots (CDs) onto TiCN nanosheets. The narrow bandgap and mixed valences of Ti and Ti endow TiCN with the capability to generate reactive oxygen species (ROS) when exposed to US, as well as the dual enzyme-like activities of peroxidase and glutathione peroxidase, which can amplify ROS levels in a cascade manner. Moreover, the catalytic activities and sonodynamic properties of the TiCN nanosheets were boosted by the formation of HJs owing to the increased speed of carrier transfer and the enhanced electron-hole separation. More importantly, the introduction of CDs with excellent NIR-II photothermal properties could achieve mild hyperthermia (43 °C) and thereby further improve the NCT and sonodynamic therapy (SDT) performances of CD/TiCN nanozymes. The synergetic therapeutic efficacy of CD/TiCN HJs through mild hyperthermia-amplified NCT and SDT could realize "three-in-one" multimodal oncotherapy to completely eliminate tumors without recurrence. This study opens a new avenue for exploring sonoresponsive and NIR-II-photoresponsive nanozymes for efficient tumor therapy based on semiconductor HJs. This article is protected by copyright. All rights reserved.