Comparative study of cationic liposomes modified with triphenylphosphonium and imidazolium surfactants for mitochondrial delivery

Mitochondria-targeting has become a major tool in the field of cancer treatment. We demonstrate how the positively charged targeting moieties can be exploited to achieve outstanding mitochondria colocalization with a comparative study of n-tetradecyltriphenylphosphonium bromide and 1-(2-hydroxyethyl)-3-tetradecyl-1H-imidazol-3-ium bromide modified liposomes. Herein, for the first time the comparative analysis of liposomes based on 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) noncovalently modified with triphenylphosphonium and imidazolium surfactants with a tetradecyl hydrocarbon tail was performed. The obtained liposomes have high stability (for more than 4 months), a significant positive charge and a high degree of encapsulation efficiency toward rhodamine B and doxorubicin hydrochloride. It was found by the methods of flow cytometry and fluorescence microscopy that modified liposomes loaded with doxorubicin hydrochloride accumulate in large numbers in duodenal adenocarcinoma (HuTu 80) and lung adenocarcinoma (A-549) tumor cells, causing dose-dependent apoptosis. The modified liposomes were loaded with a fluorescent probe rhodamine B for quantitative assessment of their colocalization with mitochondria using confocal microscopy. It was shown that not only the triphenylphosphonium cation is capable of imparting mitochondria-targeting to the nanocontainers, but also the imidazolium cation. These findings may shed additional light on the nature of mitochondria-targeting and provide a whole new ground for the development of novel cation-based mitochondria-targeting moieties.