effect of N-terminal_final.pdf (1.85 MB)
Effects of N-terminal and C-terminal modification on cytotoxicity and cellular uptake of amphiphilic cell penetrating peptides
journal contribution
posted on 2023-06-09, 09:39 authored by Mehdi Soleymani-Goloujeh, Ali Nokhodchi, Mehri Niazi, Saeedeh Najafi-Hajivar, Javid Shahbazi-Mojarrad, Nosratollah Zarghami, Parvin Zakeri-Milani, Ali Mohammadi, Mohammad Karimi, Hadi ValizadehPurpose: To assess the effect of “N-Acetylation and C-Amidation” on the cellular uptake, cytotoxicity and performance of amphiphilic Cell Penetrating Peptides loaded with MTX. Methods: Several CPPs were synthesized by solid phase peptide synthesis method. Some of these sequences were modified with Pyroglutamic acid at N-terminus and Benzylamine or memantine at C-terminus. The resultant nanomaterials were prepared due to the physical linkage between CPPs and methotrexate (MTX). The Internalization and cytotoxicity of both CPP-MTX bioconjugates and unmodified CPPs against MCF-7 cells was evaluated. Results: N-terminal and C-terminal modification did not alter the toxicity of CPPs. Physical linkage of CPPs with MTX resulted in a lower drug loading efficiency in comparison with chemically conjugated CPP-MTX bioconjugates. Both nanoparticles increase the toxic effect of MTX on MCF-7 cells. Furthermore, N-terminal and C-terminal modification may cause a tangible reduction in cellular uptake of CPPs. Conclusion: In conclusion, it was shown that cytotoxicity of modified peptides which were physically linked with MTX, considerably higher than both physically loaded unmodified peptides and chemically conjugated peptides with MTX. Also, cell internalization was reduced after peptide end-protection. These findings confirmed the effectiveness of N-terminal and C-terminal modifications on cell viability and CPPs internalization.
History
Publication status
- Published
File Version
- Accepted version
Journal
Artificial Cells, Nanomedicine, and BiotechnologyISSN
2169-141xPublisher
Informa HealthcareExternal DOI
Issue
sup1Volume
46Page range
91-103Department affiliated with
- Chemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2018-01-08First Open Access (FOA) Date
2018-12-19First Compliant Deposit (FCD) Date
2018-01-08Usage metrics
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