Metastable FeSe₂ nanosheets as a one-for-all platform for stepwise synergistic tumor therapy

The urgent need to curb the rampant rise in cancer has impelled the rapid development of nanomedicine. Under the above issue, transition metal compounds have received special attention considering their physicochemical and biochemical properties. However, how to take full advantage of the valuable characteristics of nanomaterials based on their spatial structures and chemical components for synergistic tumor therapy is a worthwhile exploration. In this work, a tailored two-dimensional (2D) FeSe₂ nanosheet (NS) platform is proposed, which integrates enzyme activity and drug efficacy through the regulation of itsstability. Specifically, metastable FeSe₂ NSs can serve as dual nanozymes in an intact state, depleting GSH and increasing ROS to induce oxidative stress in the tumor microenvironment (TME). With the gradual degradation of the FeSe₂ in TME, its degraded products can amplify the Fenton reaction and GSH consumption, enhance the expression of inflammatory factors, and achieve effective near-infrared (NIR)-light irradiation-enhanced synergistic photothermal therapy (PTT) and chemodynamic therapy (CDT). Our exploration further confirmed such a strategy that may integrate carrier activity and drug action into a metastable nanoplatform for tumor synergistic therapy. These results prompt the consideration of the rational design of a one-for-all carrier that can exhibit multifunctional properties and nanomedicine efficacy for versatile therapeutic applications in the future.