The Comparative Cytotoxic Activities of Lutein and Cisplatin in Combination with Liposomes in Relation to Breast Tumor Cells Exposed to Radiotherapy

Abstract

The interactions of the antitumor substance cisplatin and the antioxidant substance lutein with liposomes, which are considered as model membranes, have been characterized. The morphology of all liposomes was almost spherical; in the absence of the studied substances, liposomes were more evenly distributed by size and less prone to aggregation. The average size of unloaded liposomes was 617.90 ± 75.64 nm; after inclusion of cisplatin, lutein and their combination, it was 425.60 ± 64.74 nm, 877.85 ± 93.90 nm, and 189.91 ± 136.84 nm, respectively. The inclusion of cisplatin or lutein into liposomal membranes caused an increase in the zeta potential. In the presence of cisplatin in combination with lutein, the zeta potential reached the lowest values. The inclusion of cisplatin into liposomes led to a shift of the main melting point peak towards higher temperature compared to unloaded liposomes, which indicated a conformational violation of the structure of phospholipids. The addition of lutein caused the disappearance of the main endothermic peak characteristic of pure liposomes. A study by Fourier-transform infrared spectroscopy confirmed the interaction of lutein and cisplatin with functional groups of liposomes. In the absence of gamma irradiation, the IC₅₀ of lutein in the cytotoxicity test with MCF-7 cells was 10.62 μg/mL; the IC₅₀ of cisplatin was 41.02 μg/mL. The IC₅₀ of lutein and cisplatin in nanoliposomes was 65.84 and 34.29 μg/mL, respectively. In combination therapy with a dose of gamma radiation of 5 and 10 Gy, the IC₅₀ of lutein decreased from 17.0 to 9.5 μg/mL. The IC₅₀ of cisplatin changed from 51.00 to 43.09 μg/mL. This study showed that the cytotoxic effect of the standard form of lutein was stronger than that of lutein in nanoliposomes. According to this, a new therapy protocol can be proposed in which cisplatin should be replaced with lutein to increase the effectiveness of therapy against MCF-7 tumor cells.