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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\u2010modified calcium phosphate (CaP)\u2010coated, manganese\u2010doped hollow mesopores Prussian blue (MMPB) encapsulating glucose oxidase (GOx), called GOx@MMPB@CaP\u2010PEG (GMCP). GMCP with a three\u2010mode 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 Ca<jats:sup>2+<\/jats:sup> and the production of cytotoxic ROS resulting from the perfect circulation of the three\u2010mode ROS outbreak generation that Fenton\/Fenton\u2010like reaction and consumption of glutathione from Fe<jats:sup>2+<\/jats:sup>\/Fe<jats:sup>3+<\/jats:sup>and Mn<jats:sup>2+<\/jats:sup>\/Mn<jats:sup>3+<\/jats:sup> circle, and amelioration of hypoxia from MMPB\u2010guided and GOx\u2010mediated starvation therapy. Photothermal efficacy\u2010induced heat generation owing to MMPB accelerates the above reactions. Furthermore, abundant\u00a0ROS contribute to damage to mitochondria, and the calcium channels of efflux Ca<jats:sup>2+<\/jats:sup> are inhibited, resulting in a calcium overload. 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