Zhang Xiguang, Brossas Jean Yves, Parizot Christophe, Zini Jean Marc, Rebollo Angelita
CIMI Paris, Inserm 1135, UPMC, 75013 Paris, France.
Hôpital Pitié Salpêtrière, AP-HP, Department of Immunology, 75013 Paris, France.
Oncotarget. 2017 Dec 11;9(5):5944-5957. doi: 10.18632/oncotarget.23179. eCollection 2018 Jan 19.
Cell penetrating peptides (CPP) are able cross the membrane and to transport cargos, presenting a great potential in drug delivery and diagnosis. In this paper, we have identified novel natural or synthetic CPPs. We have validated their rapid and efficient time and dose-dependent penetration, the absence of toxicity, the intracellular localization and the stability to proteases degradation, one of the main bottlenecks of peptides. Moreover, we have associate a cargo (an interfering peptide blocking the association of the serine/threonine phosphatase PP2A to its inhibitor, the oncogene SET) to the new generated shuttles and showed that they new bi-functional peptides keep the original properties of the shuttle and, in addition, are able to induce apoptosis due to the properties of the cargo. The CPPs identified in this study have promising perspectives for future anti-cancer drug delivery.
细胞穿透肽(CPP)能够穿过细胞膜并运输货物,在药物递送和诊断方面具有巨大潜力。在本文中,我们鉴定了新型天然或合成的CPP。我们验证了它们快速、高效的时间和剂量依赖性穿透、无毒性、细胞内定位以及对蛋白酶降解的稳定性,蛋白酶降解是肽的主要瓶颈之一。此外,我们将一种货物(一种干扰肽,可阻断丝氨酸/苏氨酸磷酸酶PP2A与其抑制剂致癌基因SET的结合)与新生成的穿梭肽相结合,并表明这些新型双功能肽保留了穿梭肽的原始特性,此外,由于货物的特性,它们还能够诱导细胞凋亡。本研究中鉴定的CPP在未来抗癌药物递送方面具有广阔的前景。