Multivalent cell-penetrating peptides (CPPs) have been reported to show enhancement in cellular uptake and endosomolytic activity. However, its application was limited to trans-delivery of cargo which is lower in cellular uptake efficiency of cargo than cis-delivery. Here, we tried the cis-delivery of cargo with multivalent CPP by preparing bioreducible dimeric CPP–cargo with apoptotic activity using TatBim peptide, a fusion of Tat CPP and Bim peptide derived from Bim apoptosis-inducing protein. Dimeric TatBim was almost twice as highly internalized by cells and significantly induced apoptosis compared to monomeric TatBim. Contribution of bioreducible linkage of dimeric TatBim towards apoptotic activity was also confirmed.

据报道，多价细胞穿透肽（CPPs）显示出细胞摄取和内溶酶活性的增强。但是，它的应用仅限于货物的转运，其细胞的细胞吸收效率比顺式转运低。在这里，我们通过使用TatBim肽（Tat CPP和Bim凋亡诱导蛋白衍生的Bim肽的融合体）制备具有凋亡活性的可生物还原的二聚CPP-货物，尝试了多价CPP货物的顺式递送。与单体TatBim相比，二聚体TatBim被细胞高度内化的几乎两倍，并能显着诱导细胞凋亡。还证实了二聚体TatBim对细胞凋亡活性的生物可还原连接的贡献。