Effects of N-terminal and C-terminal modification on cytotoxicity and cellular uptake of amphiphilic cell penetrating peptides

摘要

Purpose: 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.udMethods: 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. udResults: 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.udConclusion: 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.