Bone is the most common organ affected by metastatic breast cancer. Targeting delivery of drugs to bone may not only enhance the treatment efficacy, but also reduce the quantity of drug administered. In order to increase the distribution of paclitaxel (PTX) in bone, herein, a novel bone metastasis-targeted glutamic hexapeptide-folic acid (Glu6-FA) derivative was designed and synthesized as liposome ligand to deliver PTX to bone metastasis effectively. The liposomes were prepared by thin film hydration method and its particle size, zeta potential, encapsulation efficiency, release profile, stability, hemolysis were also characterized. What's more, the anti-tumor effects of PTX-Glu6-FA-Lip were confirmed by the detection of cell cycle, migration, and further measurement of microtubule stabilization. In addition, the PTX-Glu6-FA-Lip showed superior targeting ability in vitro and in vivo evaluation as compared to naked PTX, non-coated, singly-modified and co-modified by physical blending liposomes. All the results suggested that Glu6-FA-modified liposome showed excellent targeting activity to metastatic bone cancer. These findings suggested that Glu6-FA-Lip was a promising bone metastasis-targeting carrier for the delivery of PTX. This study may therefore be conducive to the field of bone-targeting drugs delivery.

中文翻译：

---

谷氨酸六肽和叶酸修饰的双靶脂质体用于骨转移性乳腺癌。

骨是受转移性乳腺癌影响的最常见器官。靶向药物向骨的递送不仅可以增强治疗功效，而且可以减少给药的药物量。为了增加紫杉醇（PTX）在骨中的分布，本文中，设计了靶向骨转移的新型谷氨酸六肽-叶酸（Glu6-FA）衍生物并合成为脂质体配体，以将PTX有效地递送至骨转移。通过薄膜水化法制备脂质体，并对其粒径，ζ电位，包封率，释放曲线，稳定性，溶血性进行了表征。此外，PTX-Glu6-FA-Lip的抗肿瘤作用已通过检测细胞周期，迁移和进一步测量微管稳定性得到了证实。此外，PTX-Glu6-FA-Lip与裸露的PTX相比，在裸露的PTX，通过物理混合脂质体进行单修饰和共修饰的条件下，在体外和体内评估中均显示出优异的靶向能力。所有结果表明，Glu6-FA修饰的脂质体对转移性骨癌表现出优异的靶向活性。这些发现表明，Glu6-FA-Lip是用于PTX传递的有希望的骨转移靶向载体。因此，该研究可能有利于骨靶向药物递送领域。这些发现表明，Glu6-FA-Lip是用于PTX传递的有希望的骨转移靶向载体。因此，该研究可能有利于骨靶向药物递送领域。这些发现表明，Glu6-FA-Lip是用于PTX传递的有希望的骨转移靶向载体。因此，该研究可能有利于骨靶向药物递送领域。