Multifunctional Fe-based coordination polymer nano-bomb modified with β-lapachone and CaO2 for targeted tumor dual chemodynamic therapy with enhanced ferroptosis and H2O2 self-supply

Abstract

Chemodynamic therapy (CDT) is seriously limited by the inadequacy of exogenous catalytic ions and endogenous H₂O₂ in tumors. Herein, a multifunction nano-bomb integrated with calcium peroxide (CaO₂) and β-lapachone as donors of H₂O₂ and GSH-sensitive Fe-based coordination polymer as provider of catalytic ions was constructed for dual cascade-amplified tumor CDT. This hyaluronic acid (HA)-modified nano-bomb could be specially endocytosed by breast cancer cells through a targeting pathway, degraded and released cargoes in response to the GSH-rich cytoplasm. Furthermore, the released CaO₂ and β-lapachone could significantly self-generated sufficient H₂O₂, which could dual-cascade amplify CDT and induce severe oxidative to tumors via cooperating with the delivered iron ions from nano-bombs. Moreover, the unloaded iron and calcium ions could further accelerate tumor damage by overloading Ca²⁺ and ferroptosis, as accompanied by good magnetic resonance imaging (MRI). In vitro and in vivo studies collectively reveal that this nano-bomb not only self-initiates double cascade-amplified CDT via self-generation of H₂O₂, but also efficiently activates ferroptosis and initiates Ca²⁺ overloading, consequently significantly tumor growth suppression. This study offers a novel tumor-initiated nano-bomb for dual cascade-amplified CDT and bioimaging with activated ferroptosis and self-supplying H₂O₂.

Keywords: Chemodynamic therapy; Dual-cascade amplification; Fe-based coordination polymer; H2O2 self-supplying; Self-initiated nano-bomb.