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(H2PO3)-OH) with magnetic nanoparticles (MNPs) and electrostatic loading of chloroperoxidase (CPO). The MNPs within the nanogel can elevate H2O2 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 H2O2 into singlet oxygen (O-1(2)) in a sustained manner for neutrophil-inspired tumor therapy. As a proof of concept study, both the H2O2 and O-1(2) 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.