Valence-Transforming O₂-Depleting Nano-Assembly Enable In Situ Tumor Depositional Embolization.

Abstract

Abnormal metabolism and blood supply/O₂ imbalance in tumor cells affect drug transport delivery and increase the difficulty of tumor treatment. Controlling tumor growth by inhibiting tumor cell metabolism and regulating progressive embolization in the tumor region provides an innovative basis for constructing tumor therapeutic models. A highly biocompatible and efficient O₂-depleting agent has been investigated to enable in situ precipitation and embolization within the tumor microenvironment. In situ deformation embolizer, Fe-GA@CaCO₃ nano-assembly (GA: gallic acid), can convert into the large granular size embolization components of Fe(III) precipitates and affluent Ca²⁺ within the tumor microenvironment. In situ progressive O₂ depletion produces Fe(III) precipitates that embolize tumor regions, isolating O₂ and nutrients by blocking supply. Meanwhile, affluent Ca²⁺ acts on the intracellular, causing mitochondrial dysfunction through calcium overload and contributing to irreversible tumor cell damage. Both internal and external routes work synergistically to produce precise functional inhibition of tumors from the inside out, simultaneously responding to both intracellular and the corresponding tumor regions, providing an innovative solution for anti-tumor therapy.