Inhibition of platelet adhesion to exposed subendothelial collagen by steric hindrance with blocking peptide nanoparticles.

The inhibition of platelet adhesion to collagen in exposed vessels represents an innovative approach to the treatment of atherosclerosis and thrombosis. This study aimed to engineer peptide-based nanoparticles that prevent platelet binding to subendothelial collagen by engaging with collagen with high affinity. We examined the interactions between integrin α2/ glycoprotein VI/ von Willebrand factor A3 domain and collagen, as well as between the synthesized peptide nanoparticles and collagen, utilizing molecular dynamics simulations and empirical assays. Our findings indicated that the bond between von Willebrand factor and collagen was more robust. Specifically, the sequences SITTIDV, VDVMQRE, and YLTSEMH in von Willebrand factor were identified as essential for its attachment to collagen. Based on these sequences, three peptide nanoparticles were synthesized (BPa: Capric-GNNQQNYK-SITTIDV, BPb: Capric-GNNQQNYK-VDVMQRE, BPc: Capric-GNNQQNYK-YLTSEMH), each displaying significant affinity towards collagen. Of these, the BPa nanoparticles exhibited the most potent interaction with collagen, leading to a 75% reduction in platelet adhesion.

Ligand-receptor interaction in the specific targeting of biomimetic peptide nanoparticles to lysophosphatidylcholine.

As nanotechnology is applied clinical medicine, nanoparticle-based therapy is emerging as a novel approach for the treatment of atherosclerosis. Ligand-receptor interaction affects the effectiveness of nanoparticle targeting therapy. In this study, the biomimetic peptide (BP-KFFVLK-WYKDGD) ligand specifically targeting the lysophosphatidylcholine (LPC) receptor in atherosclerotic plaques was constructed. The corresponding ligand-receptor interaction under different pH values was investigated by molecular dynamics simulation and experimental measurements. Results show that the interaction force between the peptide and LPC is greater than that of the peptide and human umbilical vein endothelial cell, clearly demonstrating the specific targeting of the peptide ligand to the LPC receptor. The ligand-receptor binding of peptide and LPC dominantly depends on Coulomb and van der Waals interactions. The YKDG amino acids of the peptide are the main fragment that binds to LPC. Compared with neutral environment at pH 7.4, the interaction forces between the peptide and oxidized low-density lipoprotein (oxLDL) decreased by 18.22 % and 45.87 % under acidic environments at pH 6.5 and 5.5, respectively, because of the change in oxLDL secondary structure and the release of LPC from oxLDL. Nevertheless, the peptide still has a strong binding capacity with oxLDL for the treatment of atherosclerosis.

Mechanisms of deformation and drug release of targeting polypeptides based on fibronectin induction.

Polypeptide nano-carriers with deformation and sustained-release function have gained an attention in anti-tumor treatment. A multifunctional polypeptide with different motifs was discussed and the contribution of each motif to targeted drug release was analyzed by control studies. The transformation and drug release processes of polypeptides were investigated by molecular dynamics method to reveal their dynamics mechanism, and corresponding experiments were performed to verify the simulation results. We observed that the polypeptides could form NPs under the hydrophobic interaction between self-assembly motifs and the electrostatic repulsion between targeting motifs. Affected by the ligand-receptor interaction, the targeting motifs overcame the electrostatic repulsion to approach the ligand proteins, leading to the promotion of the binding of fibrous motifs and the transformation of NPs into NFs for better retention of drugs in the tumor tissues. In addition, the polypeptides with strong hydrophobicity exhibited excellent sustained-release efficiency. These insights allow drawing general conclusions contributed to the design of transformable polypeptide NPs: The decrease in the hydrophobicity of self-assembly motifs is beneficial for the enrichment of doxorubicin in tumor tissues, as well as the similar result can be obtained with the improvement of the hydrophobicity of fibrous motifs and the capability of target.

Self-assembly and disassembly mechanisms of biomimetic peptides: Molecular dynamics simulation and experimental measurement.

Drug-loaded pH-responsive nanoparticles are potential drug carriers in nanotherapeutics delivery because they can remain stable in normal tissues but can disassemble and release drug molecules in tumors. In this study, the mechanisms of self-assembly and disassembly were investigated by analyzing the characteristics of three kinds of biomimetic peptides with different components and sequences. The structural parameters and energy changes during self-assembly and disassembly were calculated by molecular dynamics simulation. Transmission electron microscopy, Fourier transform infrared spectroscopy, and atomic force microscopy were used to observe morphological changes and measure the strength of hydrophobic and hydrophilic interactions between peptides. Results show that the hydrophobic and hydrophilic interactions play crucial roles in the self-assembly and disassembly processes of peptides. The structure of the peptide clusters after self-assembly became tighter as the difference between hydrophobic and hydrophilic interactions increased, whereas a decrease in this difference led to the increased disassembly of the peptides. In general, polyethylene glycol chain modification was necessary in disassembly, and peptides with straight structures had stronger disassembly ability than that with branched structures with the same components. The morphology of peptide clusters can be controlled under different pH values by changing the composition and structure of the peptides for enhanced drug retention and sustained release.