Manganese dioxide nanosheets-based redox/pH-responsive drug delivery system for cancer theranostic application

Int J Nanomedicine. 2016 Apr 29:11:1759-78. doi: 10.2147/IJN.S98832. eCollection 2016.

Abstract

The aim of this study was to construct redox- and pH-responsive degradable manganese dioxide (MnO2) nanosheets for cancer theranostic application. The small MnO2 nanosheets were synthesized, and then functionalized by hyaluronic acid (HA), demonstrating excellent stability and tumor-targeting ability. Cisplatin (cis-diamminedichloroplatinum [CDDP]) was absorbed by the nanosheets through a physical action, which was designed as MnO2/HA/CDDP. The prepared MnO2/HA/CDDP formulation was able to efficiently deliver CDDP to tumor cells in vitro and in vivo, resulting in improved therapeutic efficiency. Subsequently, they were triggered by lower pH and higher level of reduced glutathione to generate Mn(2+), enabling magnetic resonance imaging. The smart multifunctional system combining efficient magnetic resonance imaging and chemotherapy has the potential to be used as a tumor-targeting theranostic nanomedicine.

Keywords: hyaluronic acid; magnetic resonance imaging; manganese dioxide nanosheets; theranostic application.

MeSH terms

  • A549 Cells
  • Animals
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cisplatin / pharmacokinetics
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use
  • Drug Delivery Systems / methods*
  • Drug Liberation
  • Endocytosis / drug effects
  • Humans
  • Hyaluronic Acid / chemistry
  • Hydrogen-Ion Concentration
  • Intracellular Space / metabolism
  • Magnetic Resonance Imaging
  • Manganese Compounds / chemical synthesis
  • Manganese Compounds / chemistry*
  • Mice
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Neoplasms / drug therapy*
  • Oxidation-Reduction
  • Oxides / chemical synthesis
  • Oxides / chemistry*
  • Spectroscopy, Near-Infrared
  • Theranostic Nanomedicine / methods*

Substances

  • Antineoplastic Agents
  • Manganese Compounds
  • Oxides
  • Hyaluronic Acid
  • Cisplatin
  • manganese dioxide