NIR-triggered biodegradable MOF-coated upconversion nanoparticles for synergetic chemodynamic/photodynamic therapy with enhanced efficacy

The generation of reactive oxygen species (ROS) is often limited by the overexpression of glutathione (GSH) in the tumor microenvironment (TME) and the penetration depth of visible light. In view of this, we designed biodegradable Cu/ZIF-8 shell-coated lanthanide-doped nanoparticles and loaded with a photosensitizer (Rose Bengal), and fabricated a NIR-triggered nanocomposite NaYF4:20%Yb, 2%Er@Cu/ZIF-8/RB@F127 (UCZRF) for the synergistic treatment of CDT and PDT. Interestingly, the UCZRF nanostructures can specifically release RB and Cu2+ in the acidic tumor microenvironment (TME). Cu2+ depletes GSH to effectively change the amount of ROS produced by RB under 980 nm laser irradiation, and Cu+ from the reduction reaction of GSH reacts with excess hydrogen peroxide (H2O2) in the TME to generate hydroxyl radicals (⋅OH) with high oxidation activity. In such a simple nanosystem, we enhance the anti-tumor effect of CDT and PDT by improving the efficiency of ROS generation.