Refining in vitro cytotoxicity of α-mangostin against triple-negative breast cancer using dequalinium-modified liposomal nanocarrier

Triple-negative breast cancer (TNBC) lacks estrogen, progesterone, and HER2 receptors, resulting in limited treatment options and poor outcomes. Mitochondria play vital roles in tumor progression and metastasis; thus, targeting their function with mitochondria-toxic agents, such as α-mangostin (α-M), could be an effective treatment for cancer, especially for TNBC. In this study, we attempted to develop a mitochondria-targeted nanoplatform, namely LipoDQ, containing α-M for suppressing the growth of TNBC. We first optimized the composition of the LipoDQ system to construct α-M LipoDQ following a comprehensive physical particle characterization. Subsequently, we assessed its cellular uptake and mitochondrial accumulation, utilizing flow cytometry and confocal laser scanning microscopy, respectively. Finally, we validated the cytotoxic and migratory inhibition activities of α-M LipoDQ in TNBC cells. As a result, the developed α-M LipoDQ exhibited a stable, spherical shape of 150.1 ± 4.0 nm with a uniform distribution and positive surface charge. The presence of DQ on the surface of the LipoDQ system significantly improved cellular uptake efficiency, as well as the mitochondrial accumulation of α-M. Furthermore, transfection with α-M LipoDQ significantly reduced the viability of TNBC cells compared to α-M solution or non-targeted α-M liposome. Additionally, α-M LipoDQ inhibited TNBC cell migration, indicating its potential as an alternative treatment strategy for TNBC. This finding suggests that targeting mitochondrial function in the treatment of TNBC can be beneficial and warrants further investigation in preclinical research.