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.