Cytotoxicity and Immunogenicity Evaluation of Synthetic Cell-penetrating Peptides for Methotrexate Delivery
| Author | Parvin Zakeri-Milani | en |
| Author | Saeedeh Najafi-Hajivar | en |
| Author | Muhammad Sarfraz | en |
| Author | Ali Nokhodchi | en |
| Author | Hamed Mohammadi | en |
| Author | Soheila Montazersaheb | en |
| Author | Mehri Niazi | en |
| Author | Maryam Hemmatzadeh | en |
| Author | Mehdi Soleymani-Goloujeh | en |
| Author | Behzad Baradaran | en |
| Author | Javid Shahbazi Mojarrad | en |
| Author | Masoud Farshbaf | en |
| Author | Tooba Gholikhani | en |
| Author | Hadi Valizadeh | en |
| Issued Date | 2021-07-31 | en |
| Abstract | Methotrexate (MTX) is one of the most effective therapeutics to treat different types of solid tumors; however, it suffers low permeability limiting its bioavailability and cellular uptake. To tackle this, we aim to design and fabricate different types of cell-penetrating peptides (CPPs) to improve the intracellular uptake of MTX without causing any immunogenic response. CPPs were synthesized by the solid-phase peptide synthesis method. Peptide-MTX conjugates were prepared via covalent binding of peptide and drug molecule. CPPs and peptide-E8 nanoparticles were characterized using zeta-sizer and scanning electron microscopy. Cytotoxicity of CPPs and peptide-MTX conjugates was evaluated by MTT assay. An enzyme-linked immunosorbent assay was employed to assess the IL-6 and TNF-α cytokine release profile. Amongst all sequences, W4R4-MTX possessed the highest loading efficiency (97%) and drug to peptide percentage (24.02%). The lowest loading efficiency (36%) and drug to peptide percentage (8.76%) were seen for NGRWK-MTX conjugates. The NGRWR peptide and NGRWR-E8 nanoparticles had acceptable size (~100 nm) with spherical and rod-like structures, respectively. The selected CPPs and peptide-MTX conjugates did not show any cytotoxicity or immunogenicity. The fabricated peptides are represented as promising carriers to improve the intracellular delivery of MTX to cancer cells with low immunogenic and cytotoxic effects on normal cells. | en |
| DOI | https://doi.org/10.22037/ijpr.2021.114429.14842 | en |
| Keyword | CPPs | en |
| Keyword | Drug delivery | en |
| Keyword | Nanoparticles | en |
| Keyword | Cancer | en |
| Keyword | Immune system | en |
| Publisher | Brieflands | en |
| Title | Cytotoxicity and Immunogenicity Evaluation of Synthetic Cell-penetrating Peptides for Methotrexate Delivery | en |
| Type | Original Article | en |
Files
Original bundle
1 - 1 of 1
Loading...
- Name:
- ijpr-20-506.pdf
- Size:
- 584.22 KB
- Format:
- Adobe Portable Document Format
- Description:
- Article/s PDF