A cancer-targeted nanosystem for delivery of gold(III) complexes: enhanced selectivity and apoptosis-inducing efficacy of a gold(III) porphyrin complex

Angew Chem Int Ed Engl. 2014 Nov 10;53(46):12532-6. doi: 10.1002/anie.201407143. Epub 2014 Sep 12.

Abstract

Construction of delivery systems for anticancer gold complexes to decrease their toxicity while maintaining efficacy is a key strategy to optimize and develop anticancer gold medicines. Herein, we describe cancer-targeted mesoporous silica nanoparticles (MSN) for delivery of a gold(III) porphyrin complex (Au-1 a@MSN(R)) to enhance its anticancer efficacy and selectivity between cancer and normal cells. Encapsulation of Au-1 a within mesoporous silica nanoparticles amplifies its inhibitory effects on thioredoxin reductase (TrxR), resulting in a loss of redox balance and overproduction of reactive oxygen species (ROS). Elevated cellular oxidative stress activates diversified downstream ROS-mediated signaling pathways, leading to enhanced apoptosis-inducing efficacy.

Keywords: drug delivery; gold; mesoporous materials; porphyrins; silica nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Drug Delivery Systems*
  • Humans
  • Nanoparticles / chemistry*
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Organogold Compounds / administration & dosage*
  • Organogold Compounds / pharmacology
  • Porphyrins / administration & dosage*
  • Porphyrins / pharmacology
  • Reactive Oxygen Species / metabolism
  • Silicon Dioxide / chemistry*
  • Thioredoxin-Disulfide Reductase / antagonists & inhibitors
  • Thioredoxin-Disulfide Reductase / metabolism

Substances

  • Antineoplastic Agents
  • Organogold Compounds
  • Porphyrins
  • Reactive Oxygen Species
  • Silicon Dioxide
  • Thioredoxin-Disulfide Reductase