Redox‐Active Ferrocene Quencher‐Based Supramolecular Nanomedicine for NIR‐II Fluorescence‐Monitored Chemodynamic Therapy.

Real‐time monitoring of hydroxyl radical (⋅OH) generation is crucial for both the efficacy and safety of chemodynamic therapy (CDT). Although ⋅OH probe‐integrated CDT agents can track ⋅OH production by themselves, they often require complicated synthetic procedures and suffer from self‐consumption of ⋅OH. Here, we report the facile fabrication of a self‐monitored chemodynamic agent (denoted as Fc‐CD‐AuNCs) by incorporating ferrocene (Fc) into β‐cyclodextrin (CD)‐functionalized gold nanoclusters (AuNCs) via host–guest molecular recognition. The water‐soluble CD served not only as a capping agent to protect AuNCs but also as a macrocyclic host to encapsulate and solubilize hydrophobic Fc guest with high Fenton reactivity for in vivo CDT applications. Importantly, the encapsulated Fc inside CD possessed strong electron‐donating ability to effectively quench the second near‐infrared (NIR‐II) fluorescence of AuNCs through photoinduced electron transfer. After internalization of Fc‐CD‐AuNCs by cancer cells, Fenton reaction between redox‐active Fc quencher and endogenous hydrogen peroxide (H2O2) caused Fc oxidation and subsequent NIR‐II fluorescence recovery, which was accompanied by the formation of cytotoxic ⋅OH and therefore allowed Fc‐CD‐AuNCs to in situ self‐report ⋅OH generation without undesired ⋅OH consumption. Such a NIR‐II fluorescence‐monitored CDT enabled the use of renal‐clearable Fc‐CD‐AuNCs for efficient tumor growth inhibition with minimal side effects in vivo. [ABSTRACT FROM AUTHOR]