Macrophage-membrane-coated hybrid nanoparticles with self-supplied hydrogen peroxide for enhanced chemodynamic tumor therapy

Abstract

Addressing the challenges of chemodynamic therapies (CDTs) relying on Fenton reactions in malignant tumors is an active research area. Here, we report a method to develop pH-responsive hybrid nanoparticles for enhanced chemodynamic tumor treatment. Reactive CaO₂ nanoparticles (core) are isolated by biocompatible ZIF-8 doped with Fe²⁺ (shell), and then encapsulated by macrophage membranes (symbolized as CaO₂@Fe-ZIF-8@macrophage membrane or CFZM), thus endowed with high stability under normal physiological conditions. Our design features active tumor-homing by the macrophage-membrane coating, tumor microenvironment (TME)-responsive cargo release, and self-supplied hydrogen peroxide for promotion of the Fenton reaction. We demonstrate the improved delivery/tumor cell uptake of CFZM, the efficient production of toxic ˙OH with self-supplied H₂O₂ in CFZM, and high-efficacy tumor ablation on BALB/c mice bearing CT26 tumor cells. This offers a translational strategy to develop active tumor-targeting and TME-responsive nanotherapeutics with enhanced CDT against malignant tumors.