Doxorubicin-loaded zymosan nanoparticles: Synergistic cytotoxicity and modulation of apoptosis and Wnt/β-catenin signaling pathway in C26 colorectal cancer cells

Ali Rajabi, Majid Nejati, Mina Homayoonfal, Abbas Arj, Zahra Sadat Razavi, Amirreza Ostadian, Bahareh Mohammadzadeh, Massoud Vosough, Merat Karimi, Neda Rahimian, Michael R. Hamblin, Ali Arash Anoushirvani, Hamed Mirzaei

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Zymosan is a β-glucan isolated from Saccharomyces cerevisiae that could be employed for drug delivery. We synthesized zymosan nanoparticles and measured their structural and morphological properties using XRD, UV–Vis spectroscopy, TEM and AFM. The loading of doxorubicin (DOX) onto the nanoparticles was confirmed by FT-IR, and the DOX release was shown to be pH-dependent. The effect of these agents on C26 cell viability was evaluated by MTT tests and the expression of genes connected with the Wnt/β-catenin pathway and apoptosis were analyzed by RT-qPCR and Western blotting. Treatments were able to suppress the proliferation of C26 cells, and the zymosan nanocarriers loaded with DOX enhanced the anti-proliferative effect of DOX in a synergistic manner. Zymosan nanoparticles were able to suppress the expression of cyclin D1, VEGF, ZEB1, and Twist mRNAs. Treatment groups upregulated the expression of caspase-8, while reducing the Bax/Bcl-2 ratio, thus promoting apoptosis. In conclusion, zymosan nanoparticles as DOX nanocarriers could provide a more targeted drug delivery through pH-responsiveness, and showed synergistic cytotoxicity by modifying Wnt/β-catenin signaling and apoptosis.

Original languageEnglish
Article number128949
JournalInternational Journal of Biological Macromolecules
Volume260
DOIs
Publication statusPublished - Mar 2024

Keywords

  • Apoptosis
  • Colorectal cancer
  • Doxorubicin
  • Nanoparticles
  • Wnt signaling
  • Zymosan
  • β-Glucan

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

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