Kisspeptins function as endogenous ligands for the G protein-coupled receptor GPR54. While the primary role of the Kisspeptin/GPR54 signaling pathway pertains to reproduction, several studies have shown that GPR54 is highly expressed in breast cancer, and we further confirmed this result that GPR54 expression is significantly upregulated in breast cancer cells. Based on this finding, we developed a liposomal drug delivery system utilizing the Kisspeptin/GPR54 system to treat breast cancer after confirming the safety of Kp-10-228. By surface-modifying liposomes with Kp-10-228 (228-K-EG-Liposome), we demonstrated enhanced accumulation of these liposomes in tumor cells, both in vitro and in vivo. Doxorubicin-loaded 228-K-EG-Liposome exhibited a remarkable inhibition of cancer cell proliferation, significantly extending the median survival time in mice with breast tumors compared to model mice treated with non-targeted liposomes or free doxorubicin. Our results suggest that the liposomal drug delivery system utilizing the Kisspeptin/GPR54 system is a promising novel strategy for the management of breast cancer.
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