Engineering Mg-doped CoMo-LDH as an efficient sensitizer for NIR-II light-enhanced photo-sonodynamic therapy and immune activation

Cancer remains a critical global health burden, posing a severe threat to human life. Photo-sonodynamic therapy (PSDT), which combines photodynamic (PDT) and sonodynamic (SDT) modalities, has emerged as a promising strategy to overcome limitations in tissue penetration and therapeutic precision. Despite progress, the broader application of PSDT is hindered by PDT’s potential phototoxicity/limited therapeutic penetration depth and SDT’s thermal/mechanical damage under high ultrasound (US) power, as well as the complex synthesis of sensitizers and their suboptimal reactive oxygen species (ROS) generation. Here, we engineer Mg-doped defect-rich CoMo-LDH (a-CoMgMo-LDH) nanosheets via a doping-etching strategy to address these challenges, enabling on-demand treatment from superficial to deep-seated tumors. This sensitizer exhibits exceptional dual responsiveness to NIR-II light and US. It achieves a relative singlet oxygen quantum yield (1.53) superior to most reported photosensitizers, while its sonodynamic ROS yield surpasses that of commercial TiO 2 by 22.3 times and outperforms most reported sonosensitizers, ranking among the highest reported. After bovine serum albumin (BSA) functionalization, a-CoMgMo-LDH-BSA triggers ROS-driven apoptosis and immunogenic cell death under dual irradiation, effectively suppressing tumor growth and metastasis. By integrating NIR-II-enhanced PDT/SDT into a single-component platform, this work advances precision oncology with deep-tumor targeting and immune modulation, offering a transformative strategy for clinical translation. Mg-doped defect-rich CoMo-LDH (a-CoMgMo-LDH) nanosystem is engineered through doping-etching strategy as a new photo-sonosensitizer for highly efficient photo-sonodynamic therapy, which exhibits remarkable ROS generation efficiency under NIR-II/US stimulation, achieving a 1 O 2 quantum yield of 1.53 under NIR-II light irradiation and 22.3 times ROS yields that of commercial TiO 2 under US irradiation, respectively. After bovine serum albumin (BSA) modification, a-CoMgMo-LDH-BSA efficiently kills cancer cells and eliminates tumors by inducing dual-modal ROS generation and immunogenic cell death