Tumor microenvironment responsive Mn3O4 nanoplatform for in vivo real-time monitoring of drug resistance and photothermal/chemodynamic synergistic therapy of gastric cancer

J Nanobiotechnology. 2022 May 23;20(1):240. doi: 10.1186/s12951-022-01441-6.

Abstract

Background: Postoperative chemotherapy for gastric cancer often causes multidrug resistance (MDR), which has serious consequences for therapeutic effects. Individualized treatment based on accurate monitoring of MDR will greatly improve patient survival.

Results: In this article, a self-enhanced Mn3O4 nanoplatform (MPG NPs) was established, which can react with glutathione to produce Mn2+ to enhance T1-weighted magnetic resonance imaging (MRI) and mediate in vivo real-time MDR monitoring. In vitro MRI results showed that MRI signals could be enhanced in the presence of hydrogen peroxide and glutathione and at acidic pH. In vivo MRI results indicated that MPG NPs could specifically target MDR cells, thereby realizing real-time monitoring of MDR in gastric cancer. Furthermore, MPG NPs have good chemodynamic activity, which can convert the endogenous hydrogen peroxide of tumor cells into highly toxic hydroxyl radical through Fenton-like reaction at acidic pH to play the role of chemodynamic therapy. In addition, Mn3O4 can significantly enhance the chemodynamic therapy effect because of its good photothermal conversion effect. Furthermore, in situ photothermal/chemodynamic synergistic therapy obtained remarkable results, the tumors of the mice in the synergistic therapy group gradually became smaller or even disappeared.

Conclusions: MPG NPs have good biocompatibility, providing a good nanoplatform for real-time monitoring and precise diagnosis and treatment of MDR in gastric cancer.

Keywords: Chemodynamic therapy; Fenton-like reaction; Gastric cancer; Multidrug resistance; Photothermal therapy; Self-enhanced nanoplatform.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Drug Resistance
  • Glutathione
  • Humans
  • Hydrogen Peroxide
  • Mice
  • Nanoparticles* / therapeutic use
  • Neoplasms* / drug therapy
  • Stomach Neoplasms* / drug therapy
  • Tumor Microenvironment

Substances

  • Hydrogen Peroxide
  • Glutathione