Ferrocene-containing polymersome nanoreactors for synergistically amplified tumor-specific chemodynamic therapy

Chemodynamic therapy (CDT) has been proposed to convert tumoral H2O2 into toxic hydroxyl radicals ((OH)-O-center dot) via Fenton or Fenton-like reactions for antitumor efficacy, which is frequently limited by low H2O2 concentrations or lack of enough metal ions inside tumor tissues. In this report, we present ferrocene-containing responsive polymersome nanoreactors via loading glucose oxidase (GOD) and hypoxia-activable prodrug tirapazamine (TPZ) in the inner aqueous cavities. After intravenous injection, the polymersome nanoreactors with the optimized nanoparticle size of similar to 100 nm and poly(ethylene glycol) corona facilitate tumor accumulation. The tumor acidic microenvironment can trigger the permeability of the polymersome membranes to activate the nanoreactors and release the loaded TPZ prodrugs. Tumor oxygen and glucose can enter the polymersome nanoreactors and are transformed into H2O2 under the catalysis of GOD, which are further converted into (OH)-O-center dot via Fenton reaction under catalysis of ferrocene moieties. The oxygen consumption can aggravate tumor hypoxia to activate hypoxia-responsive TPZ prodrugs which can produce benzotriazinyl (BTZ) radicals and (OH)-O-center dot. All the produced radicals synergistically kill tumor cells via the amplified CDT and suppress the tumor growth efficiently. Thus, the ferrocene-containing responsive polymersome nanoreactors loading GOD and TPZ represent a potent nano-platform to exert amplified CDT for improved anticancer efficacy.

Automated summary

By loading GOD and TPZ in responsive polymersome nanoreactors, tumor acidic microenvironment can trigger the release of TPZ prodrugs, leading to the conversion of oxygen and glucose into H2O2 under the catalysis of ferrocene and subsequent generation of (OH)• radicals. This synergistic effect efficiently kills tumor cells and suppresses tumor growth, demonstrating the potential of ferrocene-containing responsive polymersome nanoreactors as a potent nano-platform for amplified CDT.