Design of acid-activated cell-penetrating peptides with nuclear localization capacity for anticancer drug delivery,Journal of Peptide Science

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Design of acid-activated cell-penetrating peptides with nuclear localization capacity for anticancer drug delivery
Journal of Peptide Science ( IF 1.8 ) Pub Date : 2021-06-07 , DOI: 10.1002/psc.3354
Sujie Huang _{1,

2} , Zhongwen Zhu ₂ , Bo Jia ₂ , Wei Zhang ₂ , Jingjing Song ₂

Affiliation

Camptothecin (CPT), a DNA-toxin drug, exerts anticancer activity by inhibiting topoisomerase I. Targeted delivery of CPT into the cancer cell nucleus is important for enhancing its therapeutic efficiency. In this study, a new type of acid-activated cell-penetrating peptide (CPP) with nuclear localization capacity was constructed by conjugating six histidine residues and a hydrophobic peptide sequence, PFVYLI, to the nuclear localization sequence (NLS). Our results indicated that HNLS-3 displayed significant pH-dependent cellular uptake efficiency, endosomal escape ability, and nuclear localization activity. More importantly, the HNLS-3–CPT conjugate showed obviously enhanced cytotoxicity and selectivity compared with CPT. Taken together, our findings provide an effective approach to develop efficient CPPs with both cancer- and nucleus-targeting properties.

中文翻译：

具有核定位能力的酸激活细胞穿透肽的设计用于抗癌药物递送

喜树碱 (CPT) 是一种 DNA 毒素药物，通过抑制拓扑异构酶 I 发挥抗癌活性。将 CPT 靶向递送至癌细胞核对于提高其治疗效率非常重要。在这项研究中，通过将六个组氨酸残基和一个疏水肽序列PFVYLI与核定位序列（NLS）结合，构建了一种具有核定位能力的新型酸激活细胞穿透肽（CPP）。我们的结果表明，HNLS-3 显示出显着的 pH 依赖性细胞摄取效率、内体逃逸能力和核定位活性。更重要的是，与 CPT 相比，HNLS-3-CPT 偶联物显示出明显增强的细胞毒性和选择性。综合起来，

更新日期：2021-06-07

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