重新编程的代谢和活性干细胞特性有助于癌干细胞（CSCs）的存活和肿瘤发生。LXR信号途径调节不同癌症的代谢。有选择性的LXR抑制剂SR9243（SR）可以瞄准和根除非CSCs肿瘤细胞。CD133是实体瘤相关的CSCs中的一种干细胞标记物，伴随着活性脂质合成，抗CD133 mAb靶向脂质体药物递送系统有望提高药物内部化和提高贫水溶性药物治疗效果，例如SR。本研究开发了抗CD133 mAb靶向的免疫脂质体（ILipo），用于特异性地向MACS富集的CD133+ CSCs输送SR并诱导其功能作用。结果表明，平均尺寸为64.79 nm的ILipo可以最大比例地封装SR，并且细胞结合性研究显示阳离子ILipo和靶向CD133提供了CSCs的结合。另外，RhoB的FCM分析表明，相对于非靶向脂质体，ILipo摄取CD133+ CSCs的数量更多。在CD133+ CSCs中，ILipo-SR与自由SR和非靶向脂质体相比具有更显著的毒性。与Lipo-SR相比更高效的ILipo-SR改善了体外CD133+ CSCs的克隆形成能力降低、干细胞性和脂质合成降低，增强了ROS产生并诱导了细胞凋亡。我们的研究揭示了CD133和LXR的双重靶向似乎是瞄准呈现动态代谢和自我更新潜力的CD133+ CSCs的有前途的策略。©2023年。作者（s）独家许可给Springer Science+Business Media，LLC，Springer Nature的组成部分。

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.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.