Simultaneous Fenton-like Ion Delivery and Glutathione Depletion by MnO 2 -Based Nanoagent to Enhance Chemodynamic Therapy

Angew Chem Int Ed Engl. 2018 Apr 23;57(18):4902-4906. doi: 10.1002/anie.201712027. Epub 2018 Mar 23.

Abstract

Chemodynamic therapy (CDT) utilizes iron-initiated Fenton chemistry to destroy tumor cells by converting endogenous H2 O2 into the highly toxic hydroxyl radical (. OH). There is a paucity of Fenton-like metal-based CDT agents. Intracellular glutathione (GSH) with . OH scavenging ability greatly reduces CDT efficacy. A self-reinforcing CDT nanoagent based on MnO2 is reported that has both Fenton-like Mn2+ delivery and GSH depletion properties. In the presence of HCO3- , which is abundant in the physiological medium, Mn2+ exerts Fenton-like activity to generate . OH from H2 O2 . Upon uptake of MnO2 -coated mesoporous silica nanoparticles (MS@MnO2 NPs) by cancer cells, the MnO2 shell undergoes a redox reaction with GSH to form glutathione disulfide and Mn2+ , resulting in GSH depletion-enhanced CDT. This, together with the GSH-activated MRI contrast effect and dissociation of MnO2 , allows MS@MnO2 NPs to achieve MRI-monitored chemo-chemodynamic combination therapy.

Keywords: Fenton-like reaction; antitumor agents; glutathione; imaging agents; manganese dioxide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Glutathione / chemistry*
  • Humans
  • Ions / chemistry
  • Manganese Compounds / administration & dosage
  • Manganese Compounds / chemistry
  • Manganese Compounds / pharmacology*
  • Mice
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry*
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / pathology
  • Oxides / administration & dosage
  • Oxides / chemistry
  • Oxides / pharmacology*
  • Particle Size
  • Structure-Activity Relationship
  • Surface Properties

Substances

  • Antineoplastic Agents
  • Ions
  • Manganese Compounds
  • Oxides
  • Glutathione
  • manganese dioxide