Intratumoral synthesis of nano-metalchelate for tumor catalytic therapy by ligand field-enhanced coordination

Abstract

The iron gall ink-triggered chemical corrosion of hand-written documents is a big threat to Western cultural heritages, which was demonstrated to result from the iron gall (GA-Fe) chelate-promoted reactive oxygen species generation. Such a phenomenon has inspired us to apply the pro-oxidative mechanism of GA-Fe to anticancer therapy. In this work, we construct a composite cancer nanomedicine by loading gallate into a Fe-engineered mesoporous silica nanocarrier, which can degrade in acidic tumor to release the doped Fe³⁺ and the loaded gallate, forming GA-Fe nanocomplex in situ. The nanocomplex with a highly reductive ligand field can promote oxygen reduction reactions generating hydrogen peroxide. Moreover, the resultant two-electron oxidation form of GA-Fe is an excellent Fenton-like agent that can catalyze hydrogen peroxide decomposition into hydroxyl radical, finally triggering severe oxidative damage to tumors. Such a therapeutic approach by intratumoral synthesis of GA-Fe nano-metalchelate may be instructive to future anticancer researches.