Sonotherapy Using Folic Acid-Ag-Bi2O3 Nanocomposites in 2D and 3D Cultural C540 Melanoma Cells.

Abstract

Background: Sonodynamic Therapy (SDT) is increasingly recognized as an innovative, non-invasive cancer modality in which low-intensity Ultrasound (U) energizes sonosensitizers, provoking a burst of Reactive Oxygen Species (ROS) that culminate in apoptotic destruction of tumor cells.

Objective: Silver-bismuth oxide nanocomposites (AgB NCs) and their folic acid-functionalized counterparts (FAgB NCs) studied as sono-sensitizers for improving in treatment route of melanoma cancer.

Material and methods: In this experimental research, AgB NCs and FAgB NCs were synthesized via a green route using Rheum turkestanicum extract. Comprehensive physicochemical characterizations-including Field-Emission Scanning Electron Microscopy (FESEM), Energy-Dispersive X-ray spectroscopy (EDX), Ultraviolet visible spectrometer (UV-vis), Powder X-ray Diffraction (PXRD), and Fourier-Transform Infrared spectroscopy (FT-IR)-confirmed the successful formation and functionalization of the nanocomposites.

Results: (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) (MTT) assays on C540 melanoma cells revealed dose-dependent cytotoxicity, with F-AgBi NCs exhibiting significantly lower IC₅₀ values compared to AgB NCs. Upon U exposure, nanocomposites induced substantial ROS generation, mitochondrial dysfunction, and increased apoptosis, as verified by flow cytometry. Moreover, the FAgB NCs effectively suppressed cell migration and inhibited spheroid formation in 3D cultures, indicating potent antitumor activity in both monolayer and 3D models.

Conclusion: These findings underscore the synergistic potential of folic acid-functionalized AgB nanocomposites as efficient sonosensitizers for targeted melanoma therapy. Their enhanced ROS-mediated cytotoxicity, combined with folate receptor-targeted delivery, supports their application in advanced nanomedicine and SDT-based cancer treatment.