Ternary NiCoTi-layered double hydroxide nanosheets as a pH-responsive nanoagent for photodynamic/chemodynamic synergistic therapy

Combining photodynamic therapy (PDT) with chemodynamic therapy (CDT) has been proven to be a promising strategy to improve the treatment efficiency of cancer, because of the synergistic therapeutic effect arising between the two modalities. Herein, we report an inorganic nanoagent based on ternary NiCoTi-layered double hydroxide (NiCoTi-LDH) nanosheets to realize highly efficient photodynamic/chemodynamic synergistic therapy. The NiCoTi-LDH nanosheets exhibit oxygen vacancy-promoted electron-hole separation and photogenerated hole-induced O₂-independent reactive oxygen species (ROS) generation under acidic circumstances, realizing in situ pH-responsive PDT. Moreover, due to the effective conversion between Co³⁺ and Co²⁺ caused by photogenerated electrons, the NiCoTi-LDH nanosheets catalyze the release of hydroxyl radicals (·OH) from H₂O₂ through Fenton reactions, resulting in CDT. Laser irradiation enhances the catalyzed ability of the NiCoTi-LDH nanosheets to promote the ROS generation, resulting in a better performance than TiO₂ nanoparticles at pH 6.5. In vitro and in vivo experimental results show conclusively that NiCoTi-LDH nanosheets plus irradiation lead to efficient cell apoptosis and significant inhibition of tumor growth. This study reports a new pH-responsive inorganic nanoagent with oxygen vacancy-promoted photodynamic/chemodynamic synergistic performance, offering a potentially appealing clinical strategy for selective tumor elimination.