In situ assembly FeS₂-tetrathiomolybdate nanosheets for imaging-guided tumor vascular collapse and amplified catalytic therapy

Catalytic therapy has recently gained considerable attention as a novel tumor microenvironment (TME)-responsive treatment. While conventional nano-catalysts have demonstrated the ability to induce the death of tumor cells through oxidative damage via the generation of reactive oxygen species (ROS), their therapeutic efficacy is impeded by several factors, including limited tissue penetration depth and suboptimal catalytic efficiency. Herein, the FeS₂-tetrathiomolybdate (FeS₂-TTM) nanosheet was synthesized via in-situ self-assembled in the specific redox TME using metal precursors of divalent iron and tetrathiomolybdate, and these metal precursors could easily enter tumor cells through vascular penetration to avoid the blood-brain barrier. This nanosheet has been proved to possess peroxidase (POD)-like catalytic activity, which overcomes the limitations of traditional nanoparticals by the bimetallic electron transfer effect in the TME to amplify the catalytic treatment effect. Importantly, it retains the chelating copper characteristics of TTM, and inhibits tumor angiogenesis by depriving the necessary copper in cells and angiogenesis, resulting in vascular embolization to cause tumor blood vessels to collapse. Additionally, it can also act as a nanoprobe that supports both real-time fluorescence imaging monitoring and T1/T2 dual-modality magnetic resonance imaging (MRI). As a promising nanomaterial, this new type of in-situ self-assembled nanosheet provides more varieties for the construction of an integrative platform of tumor diagnosis and treatment.