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

Angew Chem Int Ed Engl. 2020 Feb 24;59(9):3732-3738. doi: 10.1002/anie.201915118. Epub 2020 Jan 21.

Abstract

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.

Keywords: bio-oxidation; cancer therapy; nanogels; reactive oxygen species; self-assembly.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chloride Peroxidase / chemistry
  • Chloride Peroxidase / metabolism*
  • Humans
  • Hydrogen Peroxide / chemistry
  • Hydrogen Peroxide / metabolism
  • Magnetic Fields
  • Magnetite Nanoparticles / chemistry*
  • Mice
  • Nanogels / chemistry*
  • Nanogels / therapeutic use
  • Nanogels / toxicity
  • Neoplasms / drug therapy
  • Neoplasms / mortality
  • Neoplasms / pathology
  • Neutrophils / chemistry
  • Neutrophils / immunology
  • Particle Size
  • Peptides / chemistry
  • Singlet Oxygen / chemistry
  • Singlet Oxygen / metabolism
  • Static Electricity
  • Survival Rate
  • Transplantation, Heterologous

Substances

  • Antineoplastic Agents
  • Magnetite Nanoparticles
  • Nanogels
  • Peptides
  • Singlet Oxygen
  • Hydrogen Peroxide
  • Chloride Peroxidase