Cancer stem cells (CSC) that may account for only a small fraction of tumor mass were found to play crucial roles during tumor initiating, progression, and metastasis. However, they are usually difficult to be treated and notoriously resilient to drug eradication. In this study, we aimed at the Wnt signaling characteristic of CSCs and designed a liposomal drug delivery system to target CSCs. Liposomes decorated with RSPO1 on the surface were constructed for specific interactions with the Wnt pathway coreceptor LGR5. Doxorubicin carried by the RSPO1-liposomes was more effective at lower concentrations than the same drug loaded in PEG-liposomes. More importantly, we showed using a patient-derived xenograft tumor model where LGR5+ CSCs coexisted with LGR5− cells, the RSPO1-liposomes were able to access more CSC cells and deliver the drug specifically and efficiently. Such a focused effect in eradicating LGR5+ cells led to massive tumor tissue necrosis and growth inhibition even when only a fraction of the conventional drug dose was used. These data clearly demonstrated the advantages of CSC-targeted drug delivery and would support the development of such approaches as a new cancer treatment strategy. Mol Cancer Ther; 17(7); 1475–85. ©2018 AACR.

中文翻译：

---

使用 RSPO 偶联多柔比星脂质体选择性靶向和根除 LGR5+ CSCs

发现可能仅占肿瘤质量一小部分的癌症干细胞 (CSC) 在肿瘤起始、进展和转移过程中发挥着至关重要的作用。然而，它们通常难以治疗，并且对药物根除具有极强的抵抗力。在这项研究中，我们针对 CSCs 的 Wnt 信号特征，设计了一种脂质体药物递送系统来靶向 CSCs。构建了表面装饰有 RSPO1 的脂质体，用于与 Wnt 通路辅助受体 LGR5 的特定相互作用。RSPO1-脂质体携带的多柔比星在较低浓度下比PEG-脂质体中装载的相同药物更有效。更重要的是，我们展示了使用患者来源的异种移植肿瘤模型，其中 LGR5+ CSC 与 LGR5− 细胞共存，RSPO1-脂质体能够接触更多的 CSC 细胞并特异性有效地递送药物。即使仅使用常规药物剂量的一小部分，这种在根除 LGR5+ 细胞方面的集中效应也会导致大量肿瘤组织坏死和生长抑制。这些数据清楚地证明了 CSC 靶向药物递送的优势，并将支持此类方法的开发，如新的癌症治疗策略。摩尔癌症治疗; 17(7); 1475-85。©2018 AACR。摩尔癌症治疗; 17(7); 1475-85。©2018 AACR。摩尔癌症治疗; 17(7); 1475-85。©2018 AACR。