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WSGC@FA@PEG/PEI-SPIONs Mitigate Chemoresistance in Gastric Adenocarcinoma by Modulating the Notch Signaling Pathway

Dongjian Song1,2, Qiuliang Liu1, Zechen Yan2,3

  • 1Department of Pediatric Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, P. R. China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|August 19, 2025
PubMed

Insights

Superparamagnetic iron oxide nanoparticles loaded with the WSGC peptide overcome chemotherapy resistance in gastric adenocarcinoma by regulating mitophagy and the Notch pathway. This offers a novel polypeptide-based cancer therapy strategy.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Gastric adenocarcinoma (GA) exhibits significant chemotherapy resistance, necessitating novel therapeutic strategies.
  • Mitochondrial homeostasis and mitophagy play crucial roles in cancer progression and drug resistance.
  • The Notch signaling pathway is implicated in various cellular processes, including cancer development.

Purpose of the Study:

  • To investigate the molecular mechanisms of WSGC peptide-loaded SPIONs (WSGC@FA@PEG/PEI-SPIONs) in overcoming chemotherapy resistance in GA.
  • To elucidate the role of these nanoparticles in regulating mitophagy and mitochondrial homeostasis via the Notch signaling pathway.
  • To evaluate the therapeutic efficacy of WSGC@FA@PEG/PEI-SPIONs in vitro and in vivo.

Main Methods:

  • Characterization of physicochemical properties of WSGC@FA@PEG/PEI-SPIONs.
  • In vitro studies assessing GA cell proliferation, migration, and invasion.
  • In vivo studies using a GA nude mouse model to evaluate tumor growth inhibition and apoptosis.

Main Results:

  • WSGC@FA@PEG/PEI-SPIONs demonstrated favorable biocompatibility and efficient peptide loading.
  • Nanoparticles significantly inhibited GA cell proliferation, migration, and invasion.
  • Downregulation of mitophagy proteins (LC3, PINK1, Parkin) and Notch pathway modulation were observed.
  • In vivo studies showed marked tumor growth inhibition and increased apoptotic activity.

Conclusions:

  • The WSGC peptide, delivered via SPIONs, effectively overcomes chemotherapy resistance in gastric adenocarcinoma.
  • Targeting mitophagy and the Notch signaling pathway presents a novel therapeutic strategy for GA.
  • WSGC@FA@PEG/PEI-SPIONs hold promise as a novel polypeptide-based cancer therapy.
Keywords:
Notch signaling pathwayWSGC Peptideschemotherapy resistancegastric adenocarcinomamitophagynanoparticles

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