Institute of Environment and Sustainable Development in Agriculture, Chinese Academy of Agricultural Sciences, Beijing, China.
College of Agriculture, Purdue University, West Lafayette, IN 47907, United States.
Curr Drug Metab. 2020;21(11):902-909. doi: 10.2174/1389200221999200820163337.
Among all cancers, lung cancer has high mortality among patients in most of the countries in the world. Targeted delivery of anticancer drugs can significantly reduce the side effects and dramatically improve the effects of the treatment. Folate, a suitable ligand, can be modified to the surface of tumor-selective drug delivery systems because it can selectively bind to the folate receptor, which is highly expressed on the surface of lung tumor cells.
This study aimed to construct a kind of folate-targeted topotecan liposomes for investigating their efficacy and mechanism of action in the treatment of lung cancer in preclinical models.
We conjugated topotecan liposomes with folate, and the liposomes were characterized by particle size, entrapment efficiency, cytotoxicity to A549 cells and in vitro release profile. Technical evaluations were performed on lung cancer A549 cells and xenografted A549 cancer cells in female nude mice, and the pharmacokinetics of the drug were evaluated in female SD rats.
The folate-targeted topotecan liposomes were proven to show effectiveness in targeting lung tumors. The anti-tumor effects of these liposomes were demonstrated by the decreased tumor volume and improved therapeutic efficacy. The folate-targeted topotecan liposomes also lengthened the topotecan blood circulation time.
The folate-targeted topotecan liposomes are effective drug delivery systems and can be easily modified with folate, enabling the targeted liposomes to deliver topotecan to lung cancer cells and kill them, which could be used as potential carriers for lung chemotherapy.
在所有癌症中，肺癌在世界上大多数国家的患者中死亡率都很高。抗癌药物的靶向递送可以显著降低副作用，并显著改善治疗效果。叶酸是一种合适的配体，可以修饰到肿瘤选择性药物递送系统的表面，因为它可以选择性地与叶酸受体结合，叶酸受体在肺癌细胞表面高度表达。
本研究旨在构建一种叶酸靶向拓扑替康脂质体，以研究其在肺癌临床前模型中的疗效和作用机制。
我们将拓扑替康脂质体与叶酸缀合，通过粒径、包封率、对 A549 细胞的细胞毒性和体外释放曲线对脂质体进行了表征。在肺癌 A549 细胞和雌性裸鼠异种移植 A549 癌细胞上进行了技术评价，并在雌性 SD 大鼠上进行了药物的药代动力学评价。
证明叶酸靶向拓扑替康脂质体能够有效地靶向肺部肿瘤。这些脂质体的抗肿瘤效果通过减少肿瘤体积和提高治疗效果得到了证明。叶酸靶向拓扑替康脂质体还延长了拓扑替康的血液循环时间。
叶酸靶向拓扑替康脂质体是有效的药物递送系统，并且可以很容易地用叶酸进行修饰，使靶向脂质体能够将拓扑替康递送到肺癌细胞并杀死它们，这可能成为肺癌化疗的潜在载体。
