In Vitro assessment of the utility of stearyl triphenyl phosphonium modified liposomes in overcoming the resistance of ovarian carcinoma Ovcar-3 cells to paclitaxel

Paclitaxel loaded in liposomes modified with stearyl triphenyl phosphonium (STPP) showed improved mitochondrial colocalization and cytotoxicity in a paclitaxel resistant cell line. The improvement in cytotoxicity was not solely due to the increased accumulation of paclitaxel in mitochondria but also due to the specific toxicity of STPP towards the resistant cell line. Mechanistic studies revealed that the cytotoxicity of STPP was associated with a decrease in mitochondrial membrane potential and other hallmarks related to caspase-independent cell death (CICD). This specific toxicity of STPP towards the paclitaxel resistant cell line was also maintained in three-dimensional in vitro spheroid cultures.

► Paclitaxel loaded in STPP-liposomes showed improved cytotoxicity in Ovcar-3 cells.
► STPP liposomes were selectively toxic to a resistant cell line.
► The mechanism of the improved cytotoxicity by STPP-liposomes is caspase-independent.
► The cell-line specific toxicity of STPP-liposomes persisted in spheroid cultures.