• • LFSs synthesized via a novel 'in situ 3D-to-2D structural transformation' strategy, transitioning from SiO–H–OSi to Fe–O bonds, offering a more convenient preparation route than conventional exfoliation methods.
• • Selective ion exchange: Interlayered Fe ions are preferentially exchanged by TME K+ (concentration >40 mM) over Na+, Mg2+, Ca2+, or Cl−, as confirmed by experiments and DFT calculations.
• • The ion-exchange-driven process activates a specific Fenton reaction in the presence of TME H+, H2O2, and glutathione, leading to highly precise catalytic therapeutic efficacy in vitro and in vivo.
• • This modality exploits the ionic exchangeability of layered silicates to reverse TME K+ disorder, offering a tumor-specific therapy with high precision and safety, potentially overcoming limitations of exogenous energy-dependent approaches.