Ultrasensitive Chemodynamic Therapy: Bimetallic Peroxide Triggers High pH‐Activated, Synergistic Effect/H2O2 Self‐Supply‐Mediated Cascade Fenton Chemistry

Abstract Recently, nanoparticle‐triggered in situ catalytic Fenton/Fenton‐like reaction is widely explored for tumor‐specific chemodynamic therapy (CDT). However, despite the great potential of CDT in tumor treatment, insensitive response to the relatively high pH of the tumor sites and the insufficient intratumoral H 2 O 2 level leads to limited efficiency of most Fenton/Fenton‐like reactions, which greatly imped its clinical conversion. This paper reports the fabrication of Fenton‐type bimetallic peroxides for ultrasensitive chemodynamic therapy with high pH‐activated, synergistic effect/H 2 O 2 self‐supply‐mediated cascade Fenton chemistry for the first time. The observations reveal that these bimetallic peroxides exhibit an ultrasensitive acid‐activated decomposition‐mediated Fenton‐like reaction at the relatively high pH of 6.5–7.0, accompanied with highly increased •OH generation efficiency (especially, 40–60‐fold increase at pH 7.0) by the metal‐mediated synergistic effect‐enhanced Fenton chemistry as well as in situ self‐generated H 2 O 2 supplement. Moreover, the bimetallic peroxides exhibit high tumor accumulation which along with a high‐efficiency tumor catalytic‐therapeutic with negligible side effects in vivo. Developing these novel bimetallic peroxides, together with the already demonstrated capacity of the key metals (Fe, Mn, Cu, etc.) for magnetic resonance imaging or photodynamic/immune‐enhanced therapy, will propel interest in development of smart high‐efficiency nanoplatform for cancer theranostics.