A smart nanoprobe with simultaneously triggering reactive oxygen species and NIR-II fluorescence for enhanced chemodynamic/photodynamic therapy and ratiometric imaging- guided tumor resection

The integration of ratiometric fluorescence imaging in the second near-infrared (NIR-II) window with chemodynamic therapy (CDT) and photodynamic therapy (PDT) represents a promising strategy for the accurate diagnosis and efficient treatment of deep tumors. In this study, we developed a smart nanoprobe, D/UCNP-MB@SiO 2 - t AuCuNCs (D/UCMSA), with simultaneously triggering reactive oxygen species (ROS) and NIR-II fluorescence for enhanced chemodynamic/ photodynamic therapy and ratiometric imaging-guided tumor resection. Upon 980 nm laser irradiation, D/UCMSA emit up-converted light at 660 nm, which activates the loaded methylene blue (MB) to produce singlet oxygen ( 1 O 2 ) for PDT. Simultaneously, the down-converted emission at 1525 nm serves as a reference signal for ratiometric imaging. The D/UCMSA surface is decorated with copper-doped gold nanoclusters ( t AuCuNCs) stabilized by triphenylphosphine-3,3′,3′′-trisulfonic acid, which undergo ligand exchange with overexpressed glutathione in the tumor microenvironment. Upon 808 nm laser excitation, this ligand exchange process activates fluorescence emission at 1085 nm. The incorporation of copper endows t AuCuNCs with peroxidase- and catalase-like activities, enabling the catalytic conversion of hydrogen peroxide (H 2 O 2 ) into hydroxyl radicals (·OH) and oxygen (O 2 ) within the tumor microenvironment. This dual enzymatic activity amplifies the CDT efficacy in tumor treatment and reshapes the tumor microenvironment, providing sufficient O 2 for 1 O 2 generation during PDT and enhancing the efficiency of combined CDT/PDT. Following with orthotopic injection of the D/UCMSA, irradiation with 808 nm and 980 nm lasers successfully enabled precise tumor resection guided via ratiometric NIR-II fluorescence imaging, combined with effective CDT/PDT. This study demonstrates a novel approach to developing integrated nanoplatforms for accurate tumor diagnosis and efficient treatment.