抗肿瘤药物的靶向递送在肿瘤治疗中尤为重要。肿瘤靶向肽是一种非常有效的肿瘤治疗药物载体。这里,我们筛选并鉴定了一种名为IHP5的高效靶向肽,该肽来源于胰岛素样生长因子结合蛋白(IGFBP).IHP5表现出对测试的肿瘤细胞系的优先结合。在各种测试的肿瘤细胞中,IHP5的递送效率高于正常细胞,特别是在人类宫颈癌细胞系HeLa中,比正常人胚胎肾细胞HEK293高11.7倍。此外,IHP5在HeLa细胞中的穿透效率是经典细胞穿透肽TAT的13倍。详细分析显示,IHP5内吞作用可能与乙酰化硫酸乙酰肝素蛋白聚糖,包括磷脂酰肌醇蛋白聚糖3(GPC3)相关,磷脂酰肌醇蛋白聚糖5(GPC5)和syndecan2(SDC2)。随后,IHP5的引入增强了天花粉蛋白(TCS)对肿瘤细胞的抑制作用,导致肿瘤细胞增加至少19倍,而在正常细胞HEK293中没有增强的细胞毒性。这些结果表明,IHP5作为一种新型的肿瘤细胞靶向穿透肽,具有靶向肿瘤细胞的能力,在药物递送应用中具有巨大的潜力。
Targeted delivery of antitumor drugs is particularly important in tumour treatment. Tumour-targeted peptide is a very effective drug carrier for tumour therapy. Here, we screened and characterised a highly efficient targeted peptide named IHP5, which was derived from insulin-like growth factor binding proteins (IGFBPs). IHP5 exhibited preferential binding to the tested tumour cell lines. The delivery efficiency of IHP5 was higher in various tested tumour cells than in normal cells, especially in the human cervical cancer cell line HeLa, which was 11.7-fold higher than in normal human embryonic kidney cells HEK293. Moreover, the penetration efficiency of IHP5 was 13 times higher than that of the classical cell penetrating peptide TAT in HeLa cells. Detail analysis revealed that IHP5 endocytosis was possibly correlated with acetylated heparan sulphate proteoglycans including phosphatidylinositol proteoglycan 3 (GPC3), phosphatidylinositol proteoglycan 5 (GPC5) and syndecan 2 (SDC2). Subsequently, the introduction of IHP5 enhanced the inhibitory effect of trichosanthin (TCS) on tumour cells, resulting in at least 19-fold increase in tumour cells without enhanced cytotoxicity in normal cells HEK293. These results suggested that IHP5, as a novel tumour cell-targeting penetrating peptide with the ability to target tumour cells, has great potential in drug delivery applications.