LXR inhibitor SR9243-loaded immunoliposomes modulate lipid metabolism and stemness in colorectal cancer cells.

Reprogrammed metabolism and active stemness contribute to cancer stem cells' (CSCs) survival and tumorigenesis. LXR signaling regulates the metabolism of different cancers. A selective LXR inhibitor, SR9243 (SR), can target and eradicate non-CSC tumor cells. CD133 is a stem marker in solid tumors-associated CSCs within the active lipogenesis, and anti-CD133 mAb targeting liposomal drug delivery systems expected to increase drug internalization and improve the therapeutic efficacy of poor-in water solubility drugs, e, g., SR. In this study, anti-CD133 mAbs-targeted Immunoliposomes (ILipo) were developed for specific delivery of SR into MACS-enriched CD133 + CSCs and induce their functional effects. Results have shown that ILipo having an average size of 64.79 nm can encapsulate SR in maximum proportion, and cell association studies have shown cationic ILipo and targeting CD133 provide the CSCs binding. Also, FCM analysis of RhoB has demonstrated that the ILipo uptake was higher in CD133 + CSCs than in the non-targeted liposomes. ILipo-SR was significantly more toxic in CD133 + CSCs compared to the free SR and non-targeted ones. More efficient than Lipo-SR, ILipo-SR improved the reduction of clonogenicity, stemness, and lipogenesis in CD133 + CSCs in vitro, boosted ROS generation, and induced apoptosis. Our study revealed the dual targeting of CD133 and LXR appears to be a promising strategy for targeting CD133 + CSCs-presenting dynamic metabolism and self-renewal potentials.