| Molecular self-assembly is the process that molecules act against each other under a series of interactions, forming highly ordered structure of supramolecular aggregates, and thus showing unique characteristics which are different from those of single molecules and small molecular aggregates. With the screening of natural bioactive peptides, meticulous design of peptide sequence and chemical modification of peptide molecules, interactions between peptides or interactions between peptide molecules and other substances can be regulated, which will affect the self-assembly behavior and is advantageous to construct several biomedical materials with certain application value. The biomedical materials constructed by peptide self-assembly are widely used in drug delivery, cell culture, tissue engineering and so on, becoming a research hotspot in recent years.In this paper, a series of research and improvement are performed on the redox-responsive peptide sequence YLKAMLEAKLMAKLMA. YLKAMLEAKLMAKLMA (MRP-1), YLKAMLEAKLMAHLMA (MRP-2), and Pal-YLKAMLEAKLMAKLMA (Pal-MRP) were synthesized by Fmoc solid phase peptide synthesis; the samples of high purity were prepared with high performance liquid phase chromatography and mass spectrometry. Firstly, gelation experiments of the three peptides were carried out at different pH values and in the redox state. The differences of secondary structures of the three peptides were defined with circular dichroism analysis. The experimental results showed that MRP-1 has response to both pH and redox. In the conditions of neutral pH or oxidation, it could quickly form hydrogel and the secondary structure of the peptide in both conditions was β-sheet. Secondly, the morphology of MRP-1 at different pH values and redox state was observed by transmission electron microscopy, atomic force microscopy, and scanning electron microscopy. Through microscopic morphology, fibrous network structure with many pores generated in neutral pH or oxidized conditions, and the diameter of the pores was approximately 5 μm. Accordingly, self-supporting peptide hydrogel came into being with certain mechanical strength in the macroscopical view. Meanwhile, the differences of the potential and particle size of the MRP-1 under at different pH values were analyzed, and the possible mechanism of pH-response might be due to the electrostatic attraction between the positive charge of lysine residues and the negative charge of glutamate residues and the interaction prompt the formation of highly ordered aggregates. Finally, the application potential of MRP-1 hydrogel was investigated. Rheological experiments showed that MRP-1 hydrogels had definite mechanical strength while G’was about 400 Pa and G" was 40 Pa. The hydrogel also possessed good self-healing ability, and could be applied to injectable biomedical materials. In addition, MRP-1 neutral hydrogel had no cytotoxicity with a 5-day MTT essay. Vitamin B12 was selected as a model drug for the construction of pH-responsive drug release system. The release rate and largest amount varied with pH and the lower the pH, the bigger release rate and largest amount. The release in neutral pH could last over 2 days and the largest release amount was only 30%.In this paper, peptide hydrogels with both response to pH and redox were constructed, and they are self-supporting with certain mechanical strength. Meanwhile, the time of hydrogelation process was very short. With good self-healing effect, no cell toxicity, the MRP-1 hydrogels have very promising developing potential and application value in drug delivery. |
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