Activatable Singlet Oxygen Generation from Lipid Hydroperoxide Nanoparticles for Cancer Therapy

Angew Chem Int Ed Engl. 2017 Jun 1;56(23):6492-6496. doi: 10.1002/anie.201701181. Epub 2017 May 4.

Abstract

Reactive oxygen species (ROS)-induced apoptosis is a widely practiced strategy for cancer therapy. Although photodynamic therapy (PDT) takes advantage of the spatial-temporal control of ROS generation, the meticulous participation of light, photosensitizer, and oxygen greatly hinders the broad application of PDT as a first-line cancer treatment option. An activatable system has been developed that enables tumor-specific singlet oxygen (1 O2 ) generation for cancer therapy, based on a Fenton-like reaction between linoleic acid hydroperoxide (LAHP) tethered on iron oxide nanoparticles (IO NPs) and the released iron(II) ions from IO NPs under acidic-pH condition. The IO-LAHP NPs are able to induce efficient apoptotic cancer cell death both in vitro and in vivo through tumor-specific 1 O2 generation and subsequent ROS mediated mechanism. This study demonstrates the effectiveness of modulating biochemical reactions as a ROS source to exert cancer death.

Keywords: apoptosis; cancer therapy; iron oxide nanoparticle; lipid hydroperoxide; singlet oxygen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Catalysis
  • Humans
  • Hydrogen-Ion Concentration
  • Iron / metabolism*
  • Linoleic Acids / metabolism*
  • Lipid Peroxides / chemistry*
  • Lipid Peroxides / metabolism
  • Mice
  • Mice, Nude
  • Nanoparticles / metabolism*
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Photochemotherapy
  • Photosensitizing Agents / therapeutic use
  • Reactive Oxygen Species / metabolism
  • Singlet Oxygen / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • Linoleic Acids
  • Lipid Peroxides
  • Photosensitizing Agents
  • Reactive Oxygen Species
  • Singlet Oxygen
  • linoleic acid hydroperoxide
  • Iron