Molybdenum oxide nanoparticles (NPs) with tunable plasmonic resonance in the near-infrared region display superior semiconducting features and photothermal properties, which are highly related to the crystalline and defective structures such as oxygen deficiencies. However, fundamental understanding on the structure-function relationship between crystalline/defective structures and photothermal properties is still unclear. To address this, herein, we have developed an "in-situ confined oxidation-reduction" strategy to regulate the defect features of molybdenum oxide NPs in the dual-mesoporous silica nanoreactor. Especially, the effects of crystalline structure/oxygen defects of molybdenum oxides on the photothermal performances were investigated by facilely tuning the amount of molybdenum resource and the reduction temperature. As a photothermal nanoagent, the optimal defective molybdenum oxide NPs encapsulated in PEGylated porous silica nanoreactor (designated as MoO 3−x @PPSNs) exhibit excellent biological stability and strong localized surface plasmon resonance effect in nearinfrared absorption range with the highest photothermal conversion efficiency up to 78.7% under 808 nm laser irradiation. More importantly, the remarkable photothermal effects of MoO 3−x @PPSNs were comprehensively demonstrated both in vitro and in vivo. Consequently, we envision that the plasmonic MoO 3−x NPs in a biocompatible porous silica nanoreactor could be used as an efficient photothermal therapy agent for photothermal ablation of tumors.

Recently, molybdenum sulfide (MoS2) has shown great application potential in tumor treatment because of its good photothermal properties. Unfortunately, most of the current molybdenum disulfide-based nanotherapeutic agents suffer from complex preparation processes, low photothermal conversion efficiencies, and poor structural/compositional regulation. To address these issues, in this paper, a facile “confined solvothermal” method is proposed to construct an MoS2-loaded porous silica nanosystem (designated as MoS2@P–hSiO2). The maximum photothermal efficiency of 79.5% of molybdenum-based materials reported in the literature at present was obtained due to the ultrasmall MoS2 nanoclusters and the rich porous channels. Furthermore, both in vitro and in vivo experiments showed that the cascade hybrid system (MoS2/GOD@P–hSiO2) after efficient loading of glucose oxidase (GOD) displayed a significant tumor-suppressive effect and good biosafety through the combined effects of photothermal and enzyme-mediated cascade catalytic therapy. Consequently, this hybrid porous network system combining the in situ solvothermal strategy of inorganic functional components and the efficient encapsulation of organic enzyme macromolecules can provide a new pathway to construct synergistic agents for the efficient and safe treatment of tumors.

Fenton/Fenton-like reactions involve the transformation of hydrogen peroxide to hydroxyl radicals to kill tumors. However, the current Fenton/Fenton-like biocatalyst always suffers from low therapeutic efficacy owing to the slow reaction rate of low-valence metal/high-valence metal cycles. Herein, a "stepwise-confined self-reduction" strategy is proposed to construct a dynamic self-reduction dual-metal (Cu/Fe) nanocatalyst in the thiols/disulfide bonds-doped micellar-organosilica framework. The preferential selfreduction of Fe and Cu sources by thiol groups and the dynamic reduction reaction between them in the confined framework produce low-valence and highly active Fe 2+ and Cu + sites in the bimetallic Cu/Fe nanoclusters. The responsively synergistic catalysis of the dual-metal nanocatalyst to generate reactive oxygen species in an acidic and reductive tumor microenvironment is evaluated. Furthermore, the cascade catalysis-induced ferroptosis mechanism through the downregulation of glutathione and glutathione peroxidase 4 protein levels and the overload of Fe 2+ is also studied. The in vitro and animal experiments demonstrate that the synergistic catalysis can significantly inhibit tumor growth while ensuring the safety of treatment. This work provides a versatile pathway for the precise construction of bioapplicable multimetalbased nanocatalysts for efficient and safe diagnosis and treatment of tumors.