溶血磷脂酸受体 1 (LPAR1) 在乳腺癌中升高。 LPAR1 的失调，包括功能和表达水平，与癌症的发生、进展和转移有关。 LPAR1 拮抗剂 AM095 或 Ki16425 可能是有效的治疗分子，但其有限的水溶性阻碍了体内递送。在这项研究中，我们报告了两种脂质体制剂的合成，其中包含 AM095 或 Ki16425，嵌入脂质双层内，作为转移性乳腺癌 (MBC) 的靶向纳米载体。数据显示，与空白脂质体制剂（对照）相比，Ki16425脂质体制剂的MBC小鼠上皮细胞（4T1）的内化增加了50%，MBC小鼠模型中的肿瘤积累增加了100%。同时，正常小鼠上皮细胞 (EpH-4Ev) 内化 Ki16425 脂质体制剂比对照制剂少 25%。分子动力学模拟表明，AM095 或 Ki16425 的整合改变了脂质双层的物理和机械特性，使其在这些脂质体制剂中比不含药物的脂质体更加灵活。将 LPAR1 拮抗剂纳入脂质体药物递送系统代表了一种针对 LPA-LPAR1 轴的可行治疗方法，这可能会阻碍 MBC 的进展。

Lysophosphatidic acid receptor 1 (LPAR1) is elevated in breast cancer. The deregulation of LPAR1, including the function and level of expression, is linked to cancer initiation, progression, and metastasis. LPAR1 antagonists, AM095 or Ki16425, may be effective therapeutic molecules, yet their limited water solubility hinders in vivo delivery. In this study, we report on the synthesis of two liposomal formulations incorporating AM095 or Ki16425, embedded within the lipid bilayer, as targeted nanocarriers for metastatic breast cancer (MBC). The data show that the Ki16425 liposomal formulation exhibited a 50% increase in internalization by MBC mouse epithelial cells (4T1) and a 100% increase in tumor accumulation in a mouse model of MBC compared with that of a blank liposomal formulation (control). At the same time, normal mouse epithelial cells (EpH-4Ev) internalized the Ki16425 liposomal formulation 25% lesser than the control formulation. Molecular dynamics simulations show that the integration of AM095 or Ki16425 modified the physical and mechanical properties of the lipid bilayer, making it more flexible in these liposomal formulations compared with liposomes without drug. The incorporation of an LPAR1 antagonist within a liposomal drug delivery system represents a viable therapeutic approach for targeting the LPA-LPAR1 axis, which may hinder the progression of MBC.