白介素-2靶向5-氟尿苷棕榈酸酯脂质体的制备及细胞毒性研究

Preparation of 5′-Palmitoyl-5-Fluorouridine Liposomes Modified with Interleukin-2 and Its Cell Toxicity

目的制备了白介素-2(IL-2)靶向5-氟尿苷棕榈酸酯(5-FURP)脂质体,并进行了体外细胞毒性,初步考察其对IL-2受体高表达的肿瘤细胞的靶向作用。方法采用逆相蒸发法制备5-FURP脂质体,通过交联剂将IL-2连接到脂质体的表面,得IL-2靶向5-FURP脂质体(IL-2-5FURP-L);UV法测定包封率;用考马斯亮蓝结合法测定IL-2与脂质体的结合率;用MTT法测定脂质体对IL-2受体高表达的皮肤T细胞淋巴瘤Hut-102细胞的生长抑制作用。结果 IL-2-5-FURP-L的粒径为180 nm;药物平均包封率为91.3%;IL-2的结合率为56.0%;在pH7.4的释放介质中,脂质体具有缓释作用;MTT实验结果显示,IL-2-5-FURP-L呈剂量依赖性抑制肿瘤细胞的生长,72 h细胞毒性试验表明IL-2-5-FURP-L对Hut-102的杀伤作用(IC50=1.04μg.mL-1)明显优于5-FURP-L(IC50=6.11μg.mL-1)及5-FURP(IC50=7.35μg.mL-1)。结论 IL-2修饰的载药脂质体具有明显的抑瘤作用和主动靶向作用。

OBJECTIVE To investigate the specificity of interleukin-2（IL-2） targeting liposomes（L） containing 5 ′-palmitoyl-5-fluorouridine（5-FURP）.METHODS Liposomes containing 5-FURP were prepared by reverse phase evaporation method.IL-2 targeting 5-FURP-L were prepared through the effect of cross linker.The entrapment efficiency was measured by UV method.The amount of IL-2 conjugated to liposomes was determined with coomassie brilliant blue binding assay.Cytotoxicity on Hut-102 cells expressing IL-2 receptors in vitro was evaluated with MTT methods.RESULTS The mean size of the liposomes was 180 nm and the entrapment efficiency was 91.3%.The coupling efficiency of IL-2 was 56.0%.In pH 7.4 PBS,5-FURP was released in a sustained manner from the liposomes.The MTT assay suggested that the IL-2 targeting 5-FURP-L had a distinct killing effect on Hut-102 tumor cells.CONCLUSION The IL-2 modified 5-FURP-L has an active targeting function and a significant anticancer effect.