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Nanoparticle mediated codelivery of nifuratel and doxorubicin for synergistic anticancer therapy through STAT3

Hailun Zheng1, Zhiwei Chen2, Aimin Cai2

  • 1Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China; Wenzhou Municipal Key Laboratory of Paediatric Pharmacy, Wenzhou, China.

Colloids and Surfaces. B, Biointerfaces
|May 17, 2020
PubMed

Insights

This study developed dual-drug nanoparticles for gastric cancer therapy. These nanoparticles effectively deliver doxorubicin and a STAT3 inhibitor, overcoming chemoresistance and enhancing apoptosis for improved treatment outcomes.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Research

Background:

  • Gastric cancer chemoresistance is a major clinical challenge.
  • Signal transducer and activator of transcription 3 (STAT3) is over-activated in gastric cancer, promoting chemoresistance.
  • Novel therapeutic strategies are needed to overcome this resistance.

Purpose of the Study:

  • To develop poly (lactic-co-glycolic acid) (PLGA) nanoparticles for co-delivery of doxorubicin (DOX) and nifuratel (NIF).
  • To evaluate the synergistic anticancer effects and underlying mechanisms of DOX and NIF co-delivery in gastric cancer cells.
  • To investigate the potential of these dual-drug nanoparticles (DNNPs) as a promising strategy against gastric cancer.

Main Methods:

  • Preparation and characterization of PLGA nanoparticles co-delivering DOX and NIF (DNNPs).
  • Evaluation of cellular uptake and cytotoxicity of DNNPs in gastric cancer cells.
  • Investigation of the mechanism of action, including apoptosis induction and STAT3 phosphorylation inhibition.

Main Results:

  • DNNPs exhibited a spherical shape and sustained drug release profiles.
  • DNNPs showed significantly increased cellular uptake and cytotoxicity compared to individual drugs.
  • DNNPs effectively induced mitochondrial-dependent apoptosis and inhibited STAT3 phosphorylation in gastric cancer cells.

Conclusions:

  • Co-delivery of DOX and NIF via PLGA nanoparticles (DNNPs) demonstrates significant synergistic anticancer effects.
  • DNNPs enhance gastric cancer therapy by inhibiting the STAT3 pathway and promoting apoptosis.
  • This nanoparticle-based strategy offers a promising approach to overcome chemoresistance in gastric cancer.
Keywords:
DoxorubicinNanoparticlesNifuratelSTAT3Synergistic effect

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