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

Int J Biol Macromol. 2024 Mar;260(Pt 2):128949. doi: 10.1016/j.ijbiomac.2023.128949. Epub 2023 Dec 22.

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.

Keywords: Apoptosis; Colorectal cancer; Doxorubicin; Nanoparticles; Wnt signaling; Zymosan; β-Glucan.

MeSH terms

  • Apoptosis
  • Colorectal Neoplasms* / drug therapy
  • Doxorubicin / chemistry
  • Humans
  • Nanoparticles* / chemistry
  • Spectroscopy, Fourier Transform Infrared
  • Wnt Signaling Pathway
  • Zymosan
  • beta Catenin / metabolism

Substances

  • Doxorubicin
  • beta Catenin
  • Zymosan