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Design of acid‐activated cell‐penetrating peptides with nuclear localization capacity for anticancer drug delivery
Author(s) -
Huang Sujie,
Zhu Zhongwen,
Jia Bo,
Zhang Wei,
Song Jingjing
Publication year - 2021
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.3354
Subject(s) - nuclear localization sequence , camptothecin , nls , nuclear transport , chemistry , cell penetrating peptide , peptide , histidine , cell , endosome , nuclear pore , biochemistry , cytotoxicity , microbiology and biotechnology , nucleus , topoisomerase , dna , cell nucleus , amino acid , biology , gene , in vitro , cytoplasm
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.