Glioma is one of the most aggressive malignant diseases for human health. It is difficult to resect completely due to their invasiveness. The targeted delivery, as a noninvasive approach, is a major strategy for the development of treatments for brain tumors. Lactoferrin (Lf) receptors are over-expressed in both brain endothelial cells and glioma cells. Macromolecular Lf modified nanoparticles have been shown to enhance the brain targeting. Muscone is a “guide” drug that have been demonstrated to promote liposomes into the brain by modification. To further enhance the brain-targeting efficacy of Lf modified carriers, we designed that Lf and muscone dual-modified liposomes cross blood–brain barrier (BBB) and target to brain for enhanced docetaxel (DTX) brain delivery. The results showed that we successfully prepared Lf and muscone dual-modified liposomes (Lf-LP-Mu-DTX), the number of Lf molecules connected to the surface of per liposome was 28. Lf-LP-Mu-DTX increased uptake in both U87-MG cells and hCMEC/D3 cells, enhanced penetration of U87-MG tumor spheroid and in vitro BBB model, had better in vitro and in vivo anti-tumor effects. In conclusion, “guide” of muscone modification enhanced brain-targeting efficacy of Lf modified liposomes, Lf and muscone dual-modified docetaxel loaded liposomes present a potential brain-targeting drug delivery system for use in the future treatment of gliomas.

中文翻译：

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麝香酮修饰“指南”增强乳铁蛋白修饰DTX脂质体的脑靶向功效和抗胶质瘤作用


胶质瘤是对人类健康最具侵袭性的恶性疾病之一。由于其侵袭性，很难完全切除。靶向递送作为一种非侵入性方法，是开发脑肿瘤治疗方法的主要策略。乳铁蛋白 (Lf) 受体在脑内皮细胞和神经胶质瘤细胞中过度表达。大分子 Lf 修饰纳米颗粒已被证明可以增强大脑靶向性。 Muscone 是一种“引导”药物，已被证明可以通过修饰促进脂质体进入大脑。为了进一步增强Lf修饰载体的脑靶向功效，我们设计了Lf和muscone双修饰脂质体穿过血脑屏障（BBB）并靶向大脑以增强多西紫杉醇（DTX）的脑递送。结果表明，我们成功制备了Lf和麝香酮双修饰脂质体（Lf-LP-Mu-DTX），每个脂质体表面连接的Lf分子数量为28个。Lf-LP-Mu-DTX均增加了摄取量。 U87-MG细胞和hCMEC/D3细胞，增强U87-MG肿瘤球体和体外BBB模型的穿透力，具有更好的体外和体内抗肿瘤效果。总之，麝香酮修饰的“指南”增强了Lf修饰脂质体的脑靶向功效，Lf和麝香酮双修饰多西紫杉醇脂质体提供了一种潜在的脑靶向药物递送系统，可用于未来的胶质瘤治疗。