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

Abstract 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 Mn 2+ and MnO 2 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 + /Mn 2+ ions perform Fenton‐like reaction with H 2 O 2 to produce cytotoxic •OH for the enhanced CDT. Cu 2+ /MnO 2 scavenge glutathione to improve the reactive oxygen species‐based therapy, while the formed Mn 2+ ions enable “turn on” magnetic resonance imaging. Significantly, O 2 is produced from the catalytic decomposition of endogenous H 2 O 2 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.