Targeted delivery of cucurbitacin B via folic acid-functionalized mesoporous silica nanoparticles for enhanced cytotoxicity and apoptosis in breast cancer

Breast cancer heterogeneity and drug resistance, particularly in triple-negative breast cancer (TNBC), present significant treatment challenges. This study developed folic acid (FA)-functionalized mesoporous silica nanoparticles (MSNs) conjugated with Cucurbitacin B (CuB-FA-MSNs), a natural triterpenoid with strong anticancer effects, to enhance targeted cytotoxicity against MCF-7 and MDA-MB-231 breast cancer cells. CuB-FA-MSNs were synthesized and characterized by dynamic light scattering (DLS), scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). The drug's release profile was investigated using in vitro testing procedures, and cytotoxicity was assessed on MCF-7, MDA-MB-231, and MCF10A cells using MTT assays. Apoptosis was analyzed with Annexin V-FITC/PI staining and flow cytometry, while real-time qPCR quantified caspase expression, and ROS generation was measured via fluorescence assay. The CuB-FA-MSNs showed an encapsulation efficiency of 86.3% and sustained CuB release for 72 h. With a uniform size of approximately 145 nm and a stable negative surface charge, they enhanced cytotoxicity in MCF-7 and MDA-MB-231 cells, achieving IC50 values of 5.69 μM and 3.4 μM, respectively, while being minimally toxic to normal cells. Apoptosis assays revealed increased apoptotic populations and upregulation of caspases-3, −8, and − 9. Treated cancer cells also showed elevated ROS levels, indicating oxidative stress as a contributing factor. The CuB-FA-MSNs enhance CuB's targeted delivery and anticancer effects on breast cancer cells by inducing apoptosis and generating ROS, while reducing toxicity to normal cells. This approach shows potential to improve treatment outcomes in resistant subtypes of mammary carcinoma and warrants further research in in vivo settings.