Ultrasound in medicine & biology · 2025
In Vitro Investigation of Targeted Sonodynamic Therapy of Melanoma Cancer Cells Utilizing a Green-Synthesized Folic Acid@CeO2-Bi2O3 Nanohybrid.
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Sarani Mina, Zahraie Niloofar, Haghighi Hanieh, Heli Hossein, Darroudi Majid, Rahi Amid, Safari Arash, Mahmoudi Tahereh, Hamidian Khadijeh, Sattarahmady Naghmeh
Аннотация
OBJECTIVE: Melanoma remains one of the most aggressive cancers, requiring innovative therapeutic approaches beyond conventional treatments. This study explores the synthesis, characterization, and therapeutic potential of cerium oxide-bismuth oxide (CeBi) and folic acid-functionalized cerium oxide-bismuth oxide (FCeBi) nanohybrids, particularly in combination with ultrasound radiation, to enhance cell toxicity in both 2D and 3D models, apoptosis, reactive oxygen species (ROS) generation, and inhibition of cancer cell migration.
METHODS: CeBi and FCeBi nanohybrids were synthesized using Rheum turkestanicum extract as a reducing agent and characterized via powder X-ray diffraction (PXRD), energy-dispersive X-ray spectroscopy (EDX), field-emission scanning electron microscopy (FESEM), Fourier-transform infrared spectroscopy (FT-IR), and UV-vis spectroscopy. The biological effects of CeBi and FCeBi nanohybrids (100 µg/mL), with and without ultrasound radiation (1.0 W cm-², 50% duty cycle, 5 min), were evaluated in melanoma (C540) cells using MTT assays, ROS generation, apoptosis analysis, migration/scratch assays, and spheroid formation studies.
RESULTS: In biological assays, synergistic treatment of FCeBi and ultrasound radiation (FCB/U+) significantly reduced melanoma cell viability, with an average survival rate of 14.9%, achieving 8% greater cancer cell eradication than ones treated with combined CeBi and ultrasound radiation (CB/U+), and 55.7% greater than FCeBi alone without ultrasound radiation. ROS production and apoptosis rates were significantly increased under ultrasound radiation. The intracellular ROS levels in the FCB+/U+ group were more than twice as high as those observed in the other treatment groups, with apoptotic cells containing 91.4%. Migration assays confirmed that FCeB/U+ resulted in the highest inhibition of cell motility, while spheroid formation was notably suppressed, indicating strong anti-tumor effects.
CONCLUSION: FCeBi nanohybrids, particularly in combination with ultrasound, demonstrated enhanced cytotoxic, apoptotic and anti-migratory effects against melanoma cells. The synergistic effects of folate receptor-mediated uptake, ultrasound-induced sonodynamic and sonoporation, and oxidative stress highlight FCeBi nanohybrids as a promising candidate for ultrasound-assisted cancer therapy, warranting further in vivo studies.
METHODS: CeBi and FCeBi nanohybrids were synthesized using Rheum turkestanicum extract as a reducing agent and characterized via powder X-ray diffraction (PXRD), energy-dispersive X-ray spectroscopy (EDX), field-emission scanning electron microscopy (FESEM), Fourier-transform infrared spectroscopy (FT-IR), and UV-vis spectroscopy. The biological effects of CeBi and FCeBi nanohybrids (100 µg/mL), with and without ultrasound radiation (1.0 W cm-², 50% duty cycle, 5 min), were evaluated in melanoma (C540) cells using MTT assays, ROS generation, apoptosis analysis, migration/scratch assays, and spheroid formation studies.
RESULTS: In biological assays, synergistic treatment of FCeBi and ultrasound radiation (FCB/U+) significantly reduced melanoma cell viability, with an average survival rate of 14.9%, achieving 8% greater cancer cell eradication than ones treated with combined CeBi and ultrasound radiation (CB/U+), and 55.7% greater than FCeBi alone without ultrasound radiation. ROS production and apoptosis rates were significantly increased under ultrasound radiation. The intracellular ROS levels in the FCB+/U+ group were more than twice as high as those observed in the other treatment groups, with apoptotic cells containing 91.4%. Migration assays confirmed that FCeB/U+ resulted in the highest inhibition of cell motility, while spheroid formation was notably suppressed, indicating strong anti-tumor effects.
CONCLUSION: FCeBi nanohybrids, particularly in combination with ultrasound, demonstrated enhanced cytotoxic, apoptotic and anti-migratory effects against melanoma cells. The synergistic effects of folate receptor-mediated uptake, ultrasound-induced sonodynamic and sonoporation, and oxidative stress highlight FCeBi nanohybrids as a promising candidate for ultrasound-assisted cancer therapy, warranting further in vivo studies.