Nanoparticles induced potent antitumor immunotherapy plays a significant role for enhancing conventional therapeutic effectiveness. However, revealing the pathway of how nanoagents themselves trigger the host immunity or how to maximize the immunotherapy efficacy still needs further exploration. Herein, rose-like MoS₂ nanoflowers modified with 2-deoxy-D-glucose (2-DG) and glucose oxidase (GOx) (MPGGFs) have been successfully fabricated via a one-pot hydrothermal reaction and following one-by-one surface modification as a multifunctional nanocatalyst for photothermal therapy enhanced self-amplified chemodynamic immunotherapy (PTT-co-CDT). By introducing GOx, the obtained MPGGFs exhibited self-amplified chemodynamic therapeutic efficacy under hypoxia tumor microenvironment (TME) because of the raised intracellular H₂O₂ level via enzyme-catalysis of oxygen. Furthermore, combined with the intrinsic excellent photothermal conversion efficiency of MoS₂ nanoflowers, PTT-co-CDT performances by MPGGFs could effectively induce the necroptosis of tumor cells both in vitro and in vivo. Then the induced necroptosis via PTT-co-CDT by MPGGFs could directly trigger host immunity by activating the antigen-specific T-cells (CD4⁺ and CD8⁺). Finally, the excellent in vivo safety of MPGGFs makes us believe that the successful construction of rose-like multifunctional nanocatalyst not only has great potentials for self-amplified chemodynamic immunotherapy, but also provides a paradigm for exploring necroptosis triggered host immunity for cancer treatment.

Molybdenum disulfide (MoS₂), a typical transition-metal dichalcogenide, has attracted increasing attention in the field of nanomedicine because of its preeminent properties. In this study, magnetic resonance imaging (MRI)-guided chemo-photothermal therapy of human breast cancer xenograft in nude mice was demonstrated using a novel core/shell structure of Fe₃O₄@MoS₂ nanocubes (IOMS NCs) via the integration of MoS₂ (MS) film onto iron oxide (IO) nanocubes through a facile hydrothermal method. After the necessary PEGylation modification of the NCs for long-circulation purposes, such PEGylated NCs were further capped by 2-deoxy-D-glucose (2-DG), a non-metabolizable glucose analogue to increase the accumulation of the as-prepared NCs at the tumor site, as 2-DG molecules could be particularly attractive to resource-hungry cancer cells. Such 2-DG-modified PEGylated NCs (IOMS-PEG-2DG NCs) acted as drug-carriers for doxorubicin (DOX), which could be easily loaded within the NCs. The obtained IOMS-PEG(DOX)-2DG NCs exhibited a T₂ relaxivity coefficient of 48.86 (mM)^-1·s^-1 and excellent photothermal performance. 24 h after intravenous injection of IOMS-PEG(DOX)-2DG NCs, the tumor site was clearly detected by enhanced T₂-weighted MRI signal. Upon exposure to an NIR 808-nm laser for 5 min at a low power density of 0.5 W·cm^-2, a marked temperature increase was noticed within the tumor site, and the tumor growth was efficiently inhibited by the chemo-photothermal effect. Therefore, our study highlights an excellent theranostic platform with great potential for targeted MRI-guided precise chemo-photothermal therapy of breast cancer.