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, NaGdF4:Yb,Tm@NaGdF4) on graphitic-phase carbon nitride (g-C3N4) 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-C3N4 and carbon dots, and the visible light from carbon dots upon UV light excitation once again activate g-C3N4 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.