TY - JOUR
T1 - Doxorubicin-loaded zymosan nanoparticles
T2 - Synergistic cytotoxicity and modulation of apoptosis and Wnt/β-catenin signaling pathway in C26 colorectal cancer cells
AU - Rajabi, Ali
AU - Nejati, Majid
AU - Homayoonfal, Mina
AU - Arj, Abbas
AU - Razavi, Zahra Sadat
AU - Ostadian, Amirreza
AU - Mohammadzadeh, Bahareh
AU - Vosough, Massoud
AU - Karimi, Merat
AU - Rahimian, Neda
AU - Hamblin, Michael R.
AU - Anoushirvani, Ali Arash
AU - Mirzaei, Hamed
N1 - Publisher Copyright:
© 2023
PY - 2024/3
Y1 - 2024/3
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Colorectal cancer
KW - Doxorubicin
KW - Nanoparticles
KW - Wnt signaling
KW - Zymosan
KW - β-Glucan
UR - http://www.scopus.com/inward/record.url?scp=85183188555&partnerID=8YFLogxK
U2 - 10.1016/j.ijbiomac.2023.128949
DO - 10.1016/j.ijbiomac.2023.128949
M3 - Article
C2 - 38143055
AN - SCOPUS:85183188555
SN - 0141-8130
VL - 260
JO - International Journal of Biological Macromolecules
JF - International Journal of Biological Macromolecules
M1 - 128949
ER -