Dual H<sub>2</sub>O<sub>2</sub>‐Amplified Nanofactory for Simultaneous Self‐Enhanced NIR‐II Fluorescence Activation Imaging and Synergistic Tumor Therapy
Ziliang Zheng, Xuejiao Chen, Yanchun Ma, Rong Dai, Shutong Wu, Tong Wang, Jun Xing, Jinnan Gao, Ruiping Zhang
Abstract
Abstract Activatable fluorescence imaging in the second near‐infrared window (NIR‐II FL, 1000–1700 nm) is of great significance for accurate tumor diagnosis and targeting therapy. However, the clinical translation of most stimulus‐activated nanoprobes is severely restricted by insufficient tumor response and out‐of‐synchronization theranostic process. Herein, an intelligent nanofactory AUC‐GOx/Cel that possesses the “external supply, internal promotion” dual H 2 O 2 ‐amplification strategy for homologous activated tumor theranostic is designed. This nanofactory is constructed via a two‐step biomineralization method using Au‐doped Ag 2 S as a carrier for glucose oxidase (GOx) and celastrol, followed by the growing of CuS to “turn off” the NIR‐II FL signal. In the overexpressed H 2 O 2 tumor‐microenvironment, the CuS featuring a responsive‐degradability behavior can effectively release Cu ions, resulting in the “ON” state of NIR‐II FL and Fenton‐like activity. The exposed GOx can realize the intratumoral H 2 O 2 supply (external supply) via the effective conversion of glucose, and mediating tumor‐starvation therapy; the interaction of celastrol and mitochondria can offer a substantial increase in the endogenous H 2 O 2 level (internal promotion), thereby significantly promoting the chemodynamic therapy (CDT) efficacy. Meanwhile, the dual H 2 O 2 ‐enhancement performance will in turn accelerate the degradation of AUC‐GOx/Cel, and achieve a positive feedback mechanism for self‐reinforcing CDT.