Microenvironment pH-Induced Selective Cell Death for Potential Cancer Therapy Using Nanofibrous Self-Assembly of a Peptide Amphiphile.
Biomacromolecules
; 22(6): 2524-2531, 2021 06 14.
Article
in En
| MEDLINE
| ID: mdl-33960189
ABSTRACT
Self-assembly of synthetic molecules has been drawing broad attention as a novel emerging approach in drug discovery. Here, we report selective cell death induced by a novel peptide amphiphile that self-assembles to form entangled nanofibers (hydrogel) based on intracellular pH (pHi). We found that a palmitoylated hexapeptide (C16-VVAEEE) formed a hydrogel below pH 7. The formation of the nanofibrous self-assembly was responsive to a small pH change around pH 7. The cytotoxicity of C16-VVAEEE was correlated with pHi of cells. Microscope observation demonstrated the self-assembly of C16-VVAEEE inside HEK293 cells. In vivo experiments revealed that the transcutaneous administration of C16-VVAEEE showed remarkable anti-tumor activity. This study proposes that distinct microenvironment inside living cells can be used as a trigger for the intracellular self-assembly of a peptide amphiphile, which provide a new clue to drug discovery.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Nanofibers
/
Neoplasms
Limits:
Humans
Language:
En
Journal:
Biomacromolecules
Journal subject:
BIOLOGIA MOLECULAR
Year:
2021
Document type:
Article
Affiliation country:
Japan