Mixed-Metal MOF-Derived Hollow Porous Nanocomposite for Trimodality Imaging Guided Reactive Oxygen Species-Augmented Synergistic Therapy

Here an excellent trimodality imaging-guided synergistic photothermal therapy (PTT)/photodynamic therapy (PDT)/chemodynamic therapy (CDT) is proposed. To this end, a mixed-metal Cu/Zn-metal-organic framework (MOF) is first assembled at room temperature on a nano-scale. Interestingly, heating the MOF results in a Cu^+/2+-coexisting hollow porous structure. Subsequent heating treatment is used to integrate Mn²⁺ and MnO₂ in the presence of manganese(II) acetylacetonate. The hollow composite achieves efficient loading of a photosensitizer, indocyanine green (ICG). Under laser irradiation, the aggregated ICG achieves photothermal imaging and PTT. Once released in the tumor site, ICG exhibits fluorescence imaging and PDT capacity. Cu⁺/Mn²⁺ ions perform Fenton-like reaction with H₂O₂ to produce cytotoxic •OH for the enhanced CDT. Cu²⁺/MnO₂ scavenge glutathione to improve the reactive oxygen species-based therapy, while the formed Mn²⁺ ions enable “turn on” magnetic resonance imaging. Significantly, O₂ is produced from the catalytic decomposition of endogenous H₂O₂ to improve ICG-mediated PDT. Moreover, photothermal-induced local hyperthermia accelerates •OH generation to enhance CDT. This synergistic drug-free antitumor strategy realizes high treatment efficacy and low side effects on normal tissues. Thus, this mixed-metal MOF is an efficient strategy to realize hollow structures for multi-function integration to improve therapeutic capacity.