Example：10.1021/acsami.1c06204 or Chem. Rev., 2007, 107, 2411-2502
Design of acid-activated cell-penetrating peptides with nuclear localization capacity for anticancer drug delivery Journal of Peptide Science (IF1.905), Pub Date : 2021-06-07, DOI: 10.1002/psc.3354 Sujie Huang, Zhongwen Zhu, Bo Jia, Wei Zhang, Jingjing Song
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.