Prussian Blue‐Derived Nanocomposite Synergized with Calcium Overload for Three‐Mode ROS Outbreak Generation to Enhance Oncotherapy

Calcium overload can lead to tumor cell death. However, because of the powerful calcium channel excretory system within tumor cells, simplistic calcium overloads do not allow for an effective antitumor therapy. Hence, the nanoparticles are created with polyethylene glycol (PEG) donor‐modified calcium phosphate (CaP)‐coated, manganese‐doped hollow mesopores Prussian blue (MMPB) encapsulating glucose oxidase (GOx), called GOx@MMPB@CaP‐PEG (GMCP). GMCP with a three‐mode enhancement of intratumor reactive oxygen species (ROS) levels is designed to increase the efficiency of the intracellular calcium overload in tumor cells to enhance its anticancer efficacy. The released exogenous Ca2+and the production of cytotoxic ROS resulting from the perfect circulation of the three‐mode ROS outbreak generation that Fenton/Fenton‐like reaction and consumption of glutathione from Fe2+/Fe3+and Mn2+/Mn3+circle, and amelioration of hypoxia from MMPB‐guided and GOx‐mediated starvation therapy. Photothermal efficacy‐induced heat generation owing to MMPB accelerates the above reactions. Furthermore, abundant ROS contribute to damage to mitochondria, and the calcium channels of efflux Ca2+are inhibited, resulting in a calcium overload. Calcium overload further increases ROS levels and promotes apoptosis of tumor cells to achieve excellent therapy. To overcome the limitation of calcium overload due to calcium channel regulation, a calcium phosphide‐coated Mn‐doped hollow Prussian blue‐derived nanocomposite with a three‐mode enhancement of intratumor cytotoxic reactive oxygen species levels is rationally designed and engineered to increase the efficiency of the intracellular calcium overload in tumor cells and synergize with it to enhance its anticancer efficacy.