Selective targeting and eradication of LGR5+ CSCs using RSPO conjugated doxorubicin liposomes

Cancer stem cells (CSCs) 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 cancer stem cells 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 co-receptor 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 Xerograft (PDX) tumor model where LGR5+ CSCs co-existed 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.

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