A Mn(III)-Sealed Metal–Organic Framework Nanosystem for Redox-Unlocked Tumor Theranostics

Here, a Mn­(III)-sealed metal–organic framework (MOF) nanosystem based on coordination between Mn­(III) and porphyrin (TCPP) via a one-pot method was designed and constructed. Mn­(III), as a sealer, not only quenched TCPP-based fluorescence but also inhibited reactive oxygen species (ROS) generation, which made MOFs an “inert” theranostic nanoparticle. Interestingly, upon endocytosis by tumor cells, MOFs were disintegrated into Mn­(II) and free TCPP by intracellular glutathione (GSH) in tumor cells, owing to redox reaction between Mn­(III) and GSH. This disintegration would lead to consumption of antioxidant GSH and activated Mn­(II)-based magnetic resonance imaging (MRI) as well as TCPP-based fluorescent imaging. More importantly, such a GSH-regulated TCPP release could implement controllable ROS generation under irradiation, which avoided side effects (inflammation and damage of normal tissues). As a consequence, after unlocking by GSH, Mn­(III)-sealed MOFs could significantly improve the therapeutic efficiency of photodynamic therapy by combining controlled ROS generation and GSH depletion after precise dual tumor homing.