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

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. The Fe‐GA@CaCO3 nano‐assembly enables a sophisticated in situ tumor embolization process by depleting oxygen and releasing Ca2+ within the tumor microenvironment. This dual‐action strategy intricately disrupts intracellular metabolic pathways and effectively obstructs nutrient supply, leading to precise, comprehensive, and potent tumor suppression, thereby offering a novel approach to tumor therapy.