Integrative in vitro – in silico evaluation of β-carotene-loaded nanoliposomes for targeted therapy against prostate carcinoma (PC-3) cells

AIMS: This study evaluated β-carotene-loaded lecithin nanoliposomes as a prostate cancer nanoplatform and assessed whether B-cell lymphoma 2 (Bcl-2) modulation could explain their activity. MATERIALS AND METHODS: Neutral multilamellar vesicles were prepared by thin-film hydration and characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential, differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy (FTIR). PC-3 cells were assessed using MTT cytotoxicity, alkaline comet assay, Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) apoptosis analysis, and cell-cycle profiling. Docking, 100 ns molecular dynamics (MD), and molecular mechanics/generalized Born surface area (MM/GBSA) analyses examined β-carotene binding to Bcl-2. RESULTS AND CONCLUSION: Encapsulation efficiency exceeded 90%. Free β-carotene showed the lowest IC50 (13.50 µg/mL), followed by liposomal β-carotene (28.26 µg/mL) and empty liposomes (36.41 µg/mL). Liposomal β-carotene produced the strongest comet-assay DNA damage and G0/G1 arrest, whereas free β-carotene induced the highest total apoptosis. Simulations showed stable hydrophobic occupation of the Bcl-2 BH3/BH1 groove. β-Carotene liposomes modulate cytotoxic kinetics and genotoxic stress, supporting optimized carotenoid nanocarriers.