Ceapro Inc V.CZO

Doxorubicin

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AEZS has run human clinical trials an enhanced doxorubcin product. It halted human trials of the enhanced product because of a lack of statistical significance vs. doxorubicin. This month there's a publication loading doxorubicin onto Zymosan which is a yeast beta glucan. "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."

Int J Biol Macromol

 

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. 2024 Mar;260(Pt 2):128949.

 doi: 10.1016/j.ijbiomac.2023.128949. Epub 2023 Dec 22.

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

Ali Rajabi 1, Majid Nejati 2, Mina Homayoonfal 3, Abbas Arj 4, Zahra Sadat Razavi 1, Amirreza Ostadian 5, Bahareh Mohammadzadeh 6, Massoud Vosough 7, Merat Karimi 8, Neda Rahimian 9, Michael R Hamblin 10, Ali Arash Anoushirvani 11, Hamed Mirzaei 12

Affiliations expand

• PMID: 38143055
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• DOI: 10.1016/j.ijbiomac.2023.128949

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.