An Electronegativity-Modulated Piezoelectric Metal-Organic Framework for Tumor Piezocatalytic Ferroptosis.

Abstract

Piezoelectric materials have emerged as versatile tools for ultrasound-triggered cancer therapy, yet their clinical application is constrained by inefficient charge separation and the limited availability of catalytic substrates in the tumor microenvironment. Here, an electronegativity-modulated piezoelectric metal-organic framework (CapMOF@HA) is reported through controlled heteroepitaxial growth of CaO₂ on pMOFs, followed by surface functionalization with hyaluronic acid (HA) for tumor-targeting capability for enhanced piezocatalytic therapy. Of note, the electronegativity-modulated heterogeneous interfaces between CaO₂ and pMOF promote the separation of electron-hole pairs while suppressing recombination through the electronegativity effect, significantly amplifying piezocatalytic reactive oxygen species (ROS) generation (•OH, ¹O₂, and •O₂⁻) under ultrasound stimulation. Furthermore, the controlled decomposition of calcium peroxide provides a continuous supply of H₂O₂ and O₂ as catalytic substrates, while releasing Ca²⁺ to induce calcium overload, triggering mitochondrial dysfunction and glutathione peroxidase 4 inhibition for ferroptosis induction. This strategy integrates enhanced piezoelectric catalysis with ferroptosis induction, overcoming long-standing limitations in piezocatalytic systems to achieve precise and robust tumor ablation. By combining substrate self-sufficiency with multifunctional therapeutic mechanisms, this work establishes tumor piezocatalytic ferroptosis as a transformative platform for next-generation piezoelectric cancer therapy.