Tuning of Peptide Cytotoxicity with Cell Penetrating Motif Activatable by Matrix Metalloproteinase-2.
ACS Omega
; 7(34): 29684-29691, 2022 Aug 30.
Article
in En
| MEDLINE
| ID: mdl-36061651
ABSTRACT
Although diverse cell penetrating motifs not only from naturally occurring proteins but also from synthetic peptides have been discovered and developed, the selectivity of cargo delivery connected to these motifs into the desired target cells is generally low. Here, we demonstrate the selective cytotoxicity tuning of an anticancer KLA peptide with a cell penetrating motif activatable by matrix metalloproteinase-2 (MMP2). The anionic masking sequence introduced at the end of the KLA peptide through an MMP2-cleavable linker is selectively cleaved by MMP2 and the cationic cell penetrating motif is activated. Upon treatment of the peptide to H1299 cells (high MMP2 level), it is selectively internalized into the cells by MMP2, which consequently induces membrane disruption and cell death. In contrast, the peptide shows negligible cytotoxicity toward A549 cancer cells with low MMP2 levels. Furthermore, the selective therapeutic efficacy of the peptide induced by MMP2 is also corroborated using in vivo study.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
ACS Omega
Year:
2022
Document type:
Article