Two‐Dimensional FePS₃ Nanosheets as an Integrative Sonosensitizer/Nanocatalyst for Efficient Nanodynamic Tumor Therapy

Abstract As the emerging modalities for tumor therapy, sonodynamic therapy (SDT) and chemodynamic therapy (CDT) can generate reactive oxygen species (ROS), typically inducing tumor cell apoptosis. However, the construction of more efficient sonosensitizers integrated with excellent Fenton/Fenton‐like catalytic activity to improve the synergistic therapeutic effect of SDT and CDT is still highly challenging. In this study, 2D semiconductor FePS₃ nanosheets (NSs), as one of the metal phosphorus trichalcogenides for both sonosensitizer and Fenton catalyst, are successfully synthesized via an ultrasonic‐assisted liquid phase exfoliation method from bulk FePS₃ and further modified with lipoic acid‐polyethylene glycol (LA‐PEG) to obtain FePS₃‐PEG NSs with desirable biocompatibility. The in vitro and in vivo results demonstrate that the engineered FePS₃‐PEG NSs induce the combinatorial SDT/CDT effect attributing to the enhanced ROS generation and significant glutathione depletion, which can conduct highly efficient and safe tumor inhibition and prolong the life span of tumor‐bearing mice. This work provides the paradigm of semiconductor FePS₃ NSs as the integrative sonosensitizer/Fenton nanocatalyst for dual nanodynamic tumor therapy, paving the new way for exploring other 2D metal phosphorus trichalcogenides in biomedicine.