Multifunctional Theranostics for Dual-Modal Photodynamic Synergistic Therapy via Stepwise Water Splitting

Combined therapy using multiple approaches has been demonstrated to be a promising route for cancer therapy. To achieve enhanced antiproliferation efficacy under hypoxic condition, here we report a novel hybrid system by integrating dual-model photodynamic therapies (dual-PDT) in one system. First, we attached core–shell structured up-conversion nanoparticles (UCNPs, NaGdF 4:Yb,Tm@NaGdF 4 ) on graphitic-phase carbon nitride ( g- C 3 N 4 ) nanosheets (one photosensitizer). Then, the as-fabricated nanocomposite and carbon dots (another photosensitizer) were assembled in ZIF-8 metal–organic frameworks through an in situ growth process, realizing the dual-photosensitizer hybrid system employed for PDT via stepwise water splitting. In this system, the UCNPs can convert deep-penetration and low-energy near-infrared light to higher-energy ultraviolet–visible emission, which matches well with the absorption range of the photosensitizers for reactive oxygen species (ROS) generation without sacrificing its efficacy under ZIF-8 shell protection. Furthermore, the UV light emitted from UCNPs allows successive activation of g -C 3 N 4 and carbon dots, and the visible light from carbon dots upon UV light excitation once again activate g -C 3 N 4 to produce ROS, which keeps the principle of energy conservation thus achieving maximized use of the light. This dual-PDT system exhibits excellent antitumor efficiency superior to any single modality, verified vividly by in vitro and in vivo assay.