Liposome-assisted combination chemotherapy improves the anti-proliferation and anti-angiogenesis response of cisplatin in breast cancer; experimental and computational study

<b>Abstract</b>Combination chemotherapy using liposomes offers a promising approach to overcome chemotherapy resistance and minimize side effects in breast cancer treatment. This study explores the synergistic effects of all-trans-retinoic acid (ATRA) and cinnamaldehyde (CA) combined with cisplatin (CPT) in MDA-MB-231 breast cancer cells. The liposomal formulation, CPT_ATRA_CA, significantly reduced cell proliferation to 25.9 ± 2.8% compared to controls and effectively inhibited angiogenesis. Additionally, it induced apoptosis, as demonstrated by flow cytometry, DAPI staining, and an elevated Bax/Bcl-2 gene expression ratio. Computational analysis via molecular docking and molecular dynamics simulation revealed that ATRA exhibited the highest binding affinity for angiogenin (ANG) with a binding energy of -106.072 kcal/mol. Experimental results, corroborated by computational data, highlight the potent anti-tumor effects of this drug trio. These findings suggest that liposomal delivery of ATRA, CA, and CPT could enhance therapeutic outcomes in breast cancer by targeting multiple pathways synergistically.