4.7 Article

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

Journal

JOURNAL OF NANOBIOTECHNOLOGY
Volume 20, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s12951-022-01441-6

Keywords

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

Funding

  1. National Natural Science Foundation of China [11727813, 32001074, 32171173]
  2. Open Funding Project of National Key Laboratory of Human Factors Engineering [SYFD061908K]
  3. Fundamental Research Funds for the Central Universities [JB211206]
  4. Shanghai Municipal Human Resources Development Program for Outstanding Young Talents in Medical and Health Sciences [2018YQ33]

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This article describes the development of a self-enhanced Mn3O4 nanoplatform for real-time monitoring and treatment of multidrug resistance (MDR) in gastric cancer. The nanoplatform can enhance TI-weighted magnetic resonance imaging (MRI) and specifically target MDR cells. It also exhibits good chemodynamic activity and photothermal conversion effect, which contribute to the treatment of MDR. In addition, in situ photothermal/chemodynamic synergistic therapy shows promising results.
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 TI -weighted magnetic resonance imaging (MRI) and mediate in vivo realtime 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.

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