Microenvironment pH-Induced Selective Cell Death for Potential Cancer Therapy Using Nanofibrous Self-Assembly of a Peptide Amphiphile
| Autor: | Tatsuo Maruyama, Sayuki Kanemitsu, Shota Yamamoto, Yuki Nishida, Atsuo Tamura, Takashi Aoi, Tomoyuki Morimoto, Kenta Morita, Kanon Nishimura |
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| Rok vydání: | 2021 |
| Předmět: |
Polymers and Plastics
Intracellular pH Nanofibers Bioengineering 02 engineering and technology 010402 general chemistry 01 natural sciences Biomaterials In vivo Neoplasms Tumor Microenvironment Materials Chemistry Peptide amphiphile Humans Cytotoxicity Cell Death Drug discovery Chemistry HEK 293 cells food and beverages Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology 0104 chemical sciences HEK293 Cells Nanofiber Biophysics lipids (amino acids peptides and proteins) Peptides 0210 nano-technology Intracellular |
| Zdroj: | Biomacromolecules. 22:2524-2531 |
| ISSN: | 1526-4602 1525-7797 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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