Cytotoxicity of Sodium Arsenite-loaded Anti-HER2 Immunoliposomes Against HER2-expressing Human Breast Cancer Cell Lines

Abstract

Background: Chemotherapy is a routine approach in treatment of patients with cancer, while side effects of chemotherapeutic drugs are inevitable. To minimize side effects, specific targeting of neoplastic cells is a promising strategy in cancer therapy. Sodium arsenite is a metalloid toxin with anti-neoplastic properties, but low selectivity and carcinogenic activity have limited its clinical usage. Methods: Targeting of HER2-overexpressing (SK-BR-3) and HER2-low expressing (MCF-7) cancerous breast cell lines by two different liposomal forms of sodium arsenite (bare liposome and trastuzumab-conjugated liposome) was investigated in the current study. Levels of HER2 expression in the above mentioned cell lines were confirmed by western blotting. Size and morphology of the constructed liposomes were characterized by atomic force microscopy (AFM) and dynamic light scattering (DLS). Viability of the cells after treatment was assessed using MTT assay. Results: Sodium arsenite in the free and liposomal forms showed growth inhibitory effects against both SK-BR-3 and MCF-7 cell lines in an examined concentration range of 1-20 µM, although this effect was more significant in SK-BR-3 cell line. Loading of sodium arsenite in anti-HER2 immunoliposomes significantly enhanced its cytotoxicity while the specificity was also improved. By encapsulation of sodium arsenite in anti-HER2 immunoliposomes, its efficacy in ablation of SKBR- 3 cells was increased about 1.4-fold compared to the free or liposomal forms. Conclusion: In conclusion, targeted delivery of sodium arsenite using anti-HER2 immunoliposomes can be considered as an alternative strategy for specific treatment of HER2-positive breast cancers.