Bi2O3@folic acid nanoparticles: An effective sonosensitizer for melanoma sonodynamic therapy

Abstract

Nanosized materials demonstrate considerable promise in sonodynamic therapy (SDT), particularly in addressing the limitations of conventional cancer treatments. This study focuses on the synthesis of bismuth oxide and folic acid (FA)-functionalized bismuth oxide NPs (FA-bismuth oxide NPs), using Rheum turkestanicum extracts as an eco-friendly method. Characterization of the synthesized NPs was performed using powder X-ray diffraction, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, Fourier-transform infrared spectroscopy, dynamic light scattering, zeta potential measurement, and UV–vis spectroscopy. Crystallite sizes of bismuth oxide and FA-bismuth oxide NPs were obtained as 43.42 and 57.90 nm, respectively, suggesting that FA incorporation facilitated particle growth. Additionally, FA modified the morphology of bismuth oxide NPs, transforming them from an amorphous structure to a conical-like shape in FA-bismuth oxide NPs. SDT effects of bismuth oxide and FA-bismuth oxide NPs on C540 (B16/F10) melanoma cells were evaluated by in vitro cytotoxicity assays, and reactive oxygen species (ROS) generation, glutathione degradation, apoptosis induction, mitochondrial membrane potential, cell migration suppression, and spheroid formation analyses. In vivo hemocompatibility in balb/c mice was also performed. Notably, FA-bismuth oxide NPs produced elevated level of ROS, leading to a marked reduction in intracellular glutathione level, and increased apoptosis via mitochondrial membrane potential decrement. The FA-bismuth oxide NPs also had in vivo hemocompatibility, and demonstrated in vitro enhanced therapeutic efficacy by significant inhibiting both cell migration and deep penetration in the spheroid. These findings established FA-bismuth oxide NPs as a highly effective sonosensitizer, offering potential advantages for SDT-based cancer treatments.