A Neutrophil-Inspired Supramolecular Nanogel for Magnetocaloric-Enzymatic Tandem Therapy

Neutrophils can responsively release reactive oxygen species (ROS) to actively combat infections by exogenous stimulus and cascade enzyme catalyzed bio-oxidation. A supramolecular nanogel is now used as an artificial neutrophil by enzymatic interfacial self-assembly of peptides (Fmoc-Tyr(H₂ PO₃ )-OH) with magnetic nanoparticles (MNPs) and electrostatic loading of chloroperoxidase (CPO). The MNPs within the nanogel can elevate H₂ O₂ levels in cancer cells under programmed alternating magnetic field (AMF) similar to the neutrophil activator, and the loaded CPO within protective peptides nanolayer converts the H₂ O₂ into singlet oxygen (¹ O₂ ) in a sustained manner for neutrophil-inspired tumor therapy. As a proof of concept study, both the H₂ O₂ and ¹ O₂ in cancer cells increase stepwise under a programmed alternating magnetic field. An active enzyme dynamic therapy by magnetically stimulated oxygen stress and sustained enzyme bio-oxidation is thus shown with studies on both cells and animals.