Self-assembling Peptide Research Articles

Short Peptides as Powerful Arsenal for Smart Fighting Cancer

Short peptides have been coming around as a strong weapon in the fight against cancer on all fronts—in immuno-, chemo-, and radiotherapy, and also in combinatorial approaches. Moreover, short peptides have relevance in cancer imaging or 3D culture. Thanks to the natural ‘smart’ nature of short peptides, their unique structural features, as well as recent progress in biotechnological and bioinformatics development, short peptides are playing an enormous role in evolving cutting-edge strategies. Self-assembling short peptides may create excellent structures to stimulate cytotoxic immune responses, which is essential for cancer immunotherapy. Short peptides can help establish versatile strategies with high biosafety and effectiveness. Supramolecular short peptide-based cancer vaccines entered clinical trials. Peptide assemblies can be platforms for the delivery of antigens, adjuvants, immune cells, and/or drugs. Short peptides have been unappreciated, especially in the vaccine aspect. Meanwhile, they still hide the undiscovered unlimited potential. Here, we provide a timely update on this highly active and fast-evolving field.

Hydrogels with Independently Controlled Adhesion Ligand Mobility and Viscoelasticity Increase Cell Adhesion and Spreading.

A primary objective in designing hydrogels for cell culture is recreating the cell-matrix interactions found within human tissues. Identifying the most important biomaterial features for these interactions is challenging because it is difficult to independently adjust variables such as matrix stiffness, stress relaxation, the mobility of adhesion ligands and the ability of these ligands to support cellular forces. In this work we designed a hydrogel platform consisting of interpenetrating polymer networks of covalently crosslinked poly(ethylene glycol) (PEG) and self-assembled peptide amphiphiles (PA). We can tailor the storage modulus of the hydrogel by altering the concentration and composition of each network, and we can tune the stress relaxation half-life through the non-covalent bonding in the PA network. Ligand mobility can be adjusted independently of the matrix mechanical properties by attaching the RGD cell adhesion ligand to either the covalent PEG network, the dynamic PA network, or both networks at once. Interestingly, our findings show that endothelial cell adhesion formation and spreading is maximized in soft, viscoelastic gels in which RGD adhesion ligands are present on both the covalent PEG and non-covalent PA networks. The dynamic nature of cell adhesion domains, coupled with their ability to exert substantial forces on the matrix, suggests that having different presentations of RGD ligands which are either mobile or are capable of withstanding significant forces are needed mimic different aspects of complex cell-matrix adhesions. By demonstrating how different presentations of RGD ligands affect cell behavior independently of viscoelastic properties, these results contribute to the rational design of hydrogels that facilitate desired cell-matrix interactions, with the potential of improving in vitro models and regenerative therapies.

The effects of self-assembling peptide on glial cell activation

The effects of self-assembling peptide on glial cell activation

Self-Assembled Peptide with Morphological Structure for Bioapplication.

Peptide materials, such as self-assembled peptide materials, are very important biomaterials. Driven by multiple interaction forces, peptide molecules can self-assemble into a variety of different macroscopic forms with different properties and functions. In recent years, the research on self-assembled peptides has made great progress from laboratory design to clinical application. This review focuses on the different morphologies, including nanoparticles, nanovesicles, nanotubes, nanofibers, and others, formed by self-assembled peptide. The mechanisms and applications of the morphology transformation are also discussed in this paper, and the future direction of self-assembled nanomaterials is envisioned.

Application of the Self-Assembling Peptide Hydrogel RADA16 for Hemostasis during Tonsillectomy: A Feasibility Study.

Tonsillectomy is a common surgical procedure but carries a high risk of readmission for secondary bleeding and pain. This study evaluated the feasibility and effectiveness of using the hemostatic self-assembling peptide hydrogel RADA16 (PuraBond, 3-D Matrix SAS; Caluire et Cuire, France) to control bleeding from the tonsillectomy wound bed. Readmission/re-operation rates were compared between a prospective case series of 21 primarily adult tonsillectomy patients treated with topical RADA16 and an untreated historical Control group of 164 patients who underwent tonsillectomy by 10 surgeons at a single tertiary hospital in the UK between March 2019 and June 2022. Cumulative readmission rates for any reason were 2-fold elevated in Control subjects (18.9%; n = 31/164 subjects) compared to patients treated intra-operatively with RADA16 hemostatic hydrogel (9.5%; n = 2/21) (p = 0.378). Readmission rates for postoperative bleeding were 3-fold higher in Controls (14.6%; n = 24/164 subjects) than in the RADA16-treated group (4.8%; n = 1/21) (p = 0.317). A similar rate of retreatment for pain was recorded in the Control (4.3%; n = 7/164) and RADA16 (4.8%; n = 1/21) groups (p = 0.999). Two Control subjects (1.2%) required re-operation for recalcitrant bleeding; no RADA16 subject (0.0%) required re-operation for any reason. No device-related adverse events occurred in the RADA16 group. Surgeons were pleased with the easy learning curve and technical feasibility associated with intra-operatively administering RADA16 hemostatic hydrogel. Intra-operative hemostasis using RADA16 peptide hydrogel was straightforward and was associated with a trend of 3-fold lower rates of readmission for postoperative bleeding events than untreated Control subjects.

Synthesis and crystal structure of a tripeptide comprising a centrally placed non-coded aromatic γ-amino acid

Abstract A protected tripeptide Boc-l-Leu-5-AIA-Aib-OMe was synthesized where 5-aminoisophthalic acid (5-AIA), a rigid non-coded aromatic γ-amino acid is incorporated as central residue. The single crystal X-ray diffraction study indicates that the peptide self-assembles into supramolecular sheet through intermolecular hydrogen bonding interaction N–H⋯O and π ··· π interaction.

Nanohydroxyapatite-Loaded, Self-Assembled Peptide Gels for Antibacterial and Osteogenic Activities

Nanohydroxyapatite-Loaded, Self-Assembled Peptide Gels for Antibacterial and Osteogenic Activities

Inhalable SPRAY nanoparticles by modular peptide assemblies reverse alveolar inflammation in lethal Gram-negative bacteria infection.

Current pharmacotherapy remains futile in acute alveolar inflammation induced by Gram-negative bacteria (GNB), eliciting consequent respiratory failure. The release of lipid polysaccharides after antibiotic treatment and subsequent progress of proinflammatory cascade highlights the necessity to apply effective inflammation management simultaneously. This work describes modular self-assembling peptides for rapid anti-inflammatory programming (SPRAY) to form nanoparticles targeting macrophage specifically, having anti-inflammation and bactericidal functions synchronously. SPRAY nanoparticles accelerate the self-delivery process in macrophages via lysosomal membrane permeabilization, maintaining anti-inflammatory programming in macrophages with efficacy close to T helper 2 cytokines. By pulmonary deposition, SPRAY nanoparticles effectively suppress inflammatory infiltration and promote alveoli regeneration in murine aseptic acute lung injury. Moreover, SPRAY nanoparticles efficiently eradicate multidrug-resistant GNB in alveoli by disrupting bacterial membrane. The universal molecular design of SPRAY nanoparticles provides a robust and clinically unseen local strategy in reverse acute inflammation featured by a high accumulation of proinflammatory cellularity and drug-resistant bacteria.

Template-assisted Flexible-to-rigid Transition of Peptides in Head-to-tail Self-polymerization Enables Sequence-controllable and Post-modifiable Peptide Nanofibers.

Peptide-based nanofibers are promising materials for many essential applications and can be generalized into two categories, self-assembling peptide nanofibers (SAPNs) and poly(amino acid) nanofibers (PAANs). Non-covalent SAPNs are sequence-controllable, but poorly stable and not suitable for post-modification. While covalent PAANs are post-modifiable, however, their sequences are either monotonic or undefined. The nanofibers obtained by head-to-tail covalent coupling polymerization of sequence-known peptides, which we call series-connected peptide nanofibers (SCPNs), promise to have the advantages of both SAPNs and PAANs, but they are barely reported. The undesired backbiting effect during the head-to-tail polymerization is one of the possible challenges. Here, we present a template-assisted strategy to trigger the flexible-to-rigid transition of peptide units, which can avoid the backbiting effect and enable consecutive intermolecular polymerization of peptides to produce desired sequence-controlled covalent SCPNs. SCPNs are highly stable and can function as excellent parent materials for various post-processing to create diverse hierarchical materials independent of the peptide sequence. Moreover, SCPNs allow for the display of predetermined functional groups at regular intervals along the nanofibers by pre-modification of the initial peptide sequence. SCPNs represent a new category of peptide-based nanofibers with outstanding performances and vast potential.

Maneuvering the mineralization of self-assembled peptide nanofibers for designing mechanically-stiffened self-healable composites toward bone-mimetic ECM.

Extracellular matrix (ECM) elasticity remains a crucial parameter to determine cell-material interactions (viz. adhesion, growth, and differentiation), cellular communication, and migration that are essential to tissue repair and regeneration. Supramolecular peptide hydrogels with their 3-dimensional porous network and tuneable mechanical properties have emerged as an excellent class of ECM-mimetic biomaterials with relevant dynamic attributes and bioactivity. Here, we demonstrate the design of minimalist amyloid-inspired peptide amphiphiles, CnPA (n = 6, 8, 10, 12) with tuneable peptide nanostructures that are efficiently biomineralized and cross-linked using bioactive silicates. Such hydrogel composites, CnBG exhibit excellent mechanical attributes and possess excellent self-healing abilities and collagen-like strain-stiffening ability as desired for bone ECM mimetic scaffold. The composites exhibited the formation of a hydroxyapatite mineral phase upon incubation in a simulated body fluid that rendered mechanical stiffness akin to the hydroxyapatite-bridged collagen fibers to match the bone tissue elasticity eventually. In a nutshell, peptide nanostructure-guided temporal effects and mechanical attributes demonstrate C8BG to be an optimal composite. Finally, such constructs feature the potential for adhesion, proliferation of U2OS cells, high alkaline phosphatase activity, and osteoconductivity.

Mechanically rigid metallopeptide nanostructures achieved by highly efficient folding

AbstractNatural proteins must fold into complex three-dimensional structures to achieve excellent mechanical properties vital for biological functions, but this has proven to be exceptionally difficult to control in synthetic systems. As such, the long-standing issue of low mechanical rigidity and stability induced by misfolding constrains the physical and chemical properties of self-assembling peptide materials. Here we introduce a mixed-chirality strategy that enhances folding efficiency in topologically interlocked metallopeptide nanostructures. The orderly entanglement of heterochiral peptide-derived linkers can fold into a compact three-dimensional catenane. These folding-mediated secondary structural changes not only generate biomimetic binding pockets derived from individual peptide strands but also result in strong chiral amplification by the tight interlocking manner. Notably, this strategic ‘chirality mutation’ alters their arrangement into tertiary structures and is pivotal in achieving exceptional mechanical rigidity observed in the metallopeptide crystals, which exhibit a Young’s modulus of 157.6 GPa, approximately tenfold higher than the most rigid proteinaceous materials in nature. This unusual nature is reflected in enhanced peptide-binding properties and heightened antimicrobial activities relative to its unfolded counterpart.

A Membrane-Anchoring Self-Assembling Peptide Allows Bioorthogonal Coupling of Type-I AIEgens for Pyroptosis-Induced Cancer Therapy.

Enrichment of photosensitizers (PSs) on cancer cell membranes via bioorthogonal reactions is considered to be a very promising therapeutic modality. However, azide-modified sugars-based metabolic labeling processes usually lack targeting and the labeling speed is relatively slow. Moreover, it has been rarely reported that membrane-anchoring pure type-I PSs can induce cancer cell pyroptosis. Here, we report an alkaline phosphatase (ALP) and cholecystokinin-2 receptor (CCK2R) dual-targeting peptide named DBCO-pYCCK6, which can selectively and rapidly self-assemble on cancer cell membrane, and then bioorthogonal enrich type-I aggregation-induced emission luminogens (AIEgen) PSs (SAIE-N3) on the cell membrane. Upon light irradiation, the membrane-anchoring SAIE-N3 could effectively generate type-I reactive oxygen species (ROS) to induce gasdermin E (GSDME)-mediated pyroptosis. In vivo experiments demonstrated that the bioorthogonal combination strategy of peptide and AIEgen PSs could significantly inhibit tumor growth, which is accompanied by CD8+ cytotoxic T cell infiltration. This work provides a novel self-assembly peptide-mediated bioorthogonal reaction strategy to bridge the supramolecular self-assembly and AIE field through strain-promoted azide-alkyne cycloaddition (SPAAC) and elucidates that pure type-I membrane-anchoring PSs can be used for cancer therapy via GSDME-mediated pyroptosis.

Self-assembling Peptides (SAPs) as Powerful Tools for the Preparation of Antimicrobial and Wound-Healing Nanostructures

: Supramolecular self-assembly (SA) is a naturally occurring and free energy-driven process of molecules to produce nanostructured systems depending on the assembling environment. SA molecules have captivated the research attention since they possess singular physicochemical properties that are potentially useful to make the nanostructures quite suitable for biomedical applications, such as diagnostics, drug delivery, tissue engineering, and regenerative medicine. Due to their high biological activity and low toxicity, the self-assembly properties of peptides bid certain advantages as drugs and drug delivery platforms. Among the discovered self-assembling bioactive peptides (SAPs), antimicrobial peptides (AMPs) are widely distributed through plant and animal kingdoms and play a key role as an alternative strategy to fight infections bypassing conventional antimicrobial drugs, susceptible to antimicrobial resistance. Based on this evidence, in this review, we summarized the mechanism of the self-assembling of peptides, the main forces responsible for the SAPs formation, and the studies regarding their possible implication in infectious diseases as well as wound dressing materials.

Influence of Self-Assembly Peptides Usage in Combination with Fluorides and Calcium Phosphate Compounds upon Remineralization for Incipient Carious Lesions

Influence of Self-Assembly Peptides Usage in Combination with Fluorides and Calcium Phosphate Compounds upon Remineralization for Incipient Carious Lesions

Neurophilic peptide-reinforced dual-fiber-network bioactive hydrogels for spinal cord injury repair

Spinal cord injury (SCI) is a challenging central nervous system disorder that characterized by microenvironmental disturbances following injury, which can be addressed by simulating the microenvironment of the spinal cord regeneration. Herein, we report the design and synthesis of bioactive hydrogels with a dual-fiber-network (DFN) porous structure, using self-assembled peptide nanofibers (PNFs) and natural cellulose nanofibers (CNFs). A neurophilic peptide is further introduced to enhance nervous regeneration capability of the pre-prepared PNF/CNF hydrogels, which then exhibit excellent neuro-affinity, self-healing ability, biodegradability, and biocompatibility, facilitating targeted SCI repair and regeneration through the hydrogel injection. The in vitro experiments reveal that the DFN hydrogel can enhance the proliferation and migration of bone marrow mesenchymal stem cells, and induce neural stem cell (NSC) proliferation with enhanced neuronal differentiation and axonal growth. Additionally, the in vivo studies validate that the hydrogel attenuates the post-SCI inflammation, inhibits reactive astrocyte proliferation, and facilitates endogenous NSC proliferation and migration, as well as promotes neuronal growth and axonal regeneration. The potential mechanism of SCI repair is ascribed to the hydrogel-induced activation of the PI3K/AKT/mTOR pathway, which alleviates inflammatory response, inhibits excessive reactive response of glial cells, and promotes NSC differentiation into neurons. This neurophilic peptide-reinforced DFN bioactive hydrogel system, with its comprehensive approach to SCI repair, holds great potential for clinical applications.

Scaffold loaded LPS-hUCMSC-sEVs promote Osteo/odontogenic differentiation and angiogenic potential of hDPSCs

ObjectiveThe formation of dentin-pulp complex determines the success of vital pulp therapy. Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles (hUCMSC-sEVs) appeared to have stronger effect in anti-inflammatory and promoting the proliferation and migration of human dental pulp stem cells (hDPSCs). Moreover, Lipopolysaccharides (LPS) pretreatment can enhance the rapeutic potency of extracellular vesicles. LPS pretreatment hUCMSC-sEVs have the potential to regenerate the dentin-pulp complex by recruiting hDPSCs. This paper aims to develop collagen sponge/self-assembling peptide nanofiber scaffold (CS/SAPNS) composite scaffold loaded with LPS pretreatment hUCMSC-sEVs (CS/SAPNS-sEVs), and assess the release characteristics of hUCMSC-sEVs and the effect of this composite scaffold on osteo/odontogenic differentiation and angiogenic potential in hDPSCs. MethodsLPS pretreatment hUCMSC-sEVs (LPS-hUCMSC-sEVs) were mixed with self-assembling peptide hydrogel and loaded onto collagen sponge to obtain the CS/SAPNS-sEVs. BCA assay, nanoparticle analysis, transmission electron microscopy and laser confocal microscopy were used to investigate the characteristics of LPS-hUCMSC-sEVs loaded on CS/SAPNS. Osteo/odontogenic differentiation ability of hDPSCs were analyzed by ALP stainning, alizarin red staining. RT-PCR and Western blot analysis were performed to confirm the levels of osteo/odontogenic factors and angiogenic factors, and the involvement of NF-κB pathway was verified by immunocytochemical staining and Western blot analysis. ResultsCS/SAPNS could control LPS-hUCMSC-sEVs release for 7 days and keep their structural integrity. CS/SAPNS-sEVs promoted deposition of calcified nodules and expression of osteogenic/odontogenic and angiogenic factors in hDPSCs. On the contrary, inhibition of the NF-κB pathway down-regulated the expression of CS/SAPNS-sEVs-regulated osteo/odontogenic and angiogenic factors. ConclusionCS/SNAPS could be used as scaffold for LPS-hUCMSC-sEVs, and CS/SAPNS-sEVs may promote osteo/odontogenic differentiation and enhance the angiogenic potential of hDPSCs through activating the NF-κB pathway.

Evaluation of the effect of self-assembling peptide and fluoride varnish, alone or in combination with laser irradiation, on artificial enamel caries: a SEM/EDS and Micro-CT study.

The aim of this study was to investigate the effect of remineralization agents such as fluoride varnish and P11-4, alone and in combination with Er: YAG laser, on in-vitro hard tissue repair in artificial enamel lesions. A total of sixty enamel surfaces of 4 × 5mm in size were created on both the buccal and lingual sides of thirty extracted wisdom teeth. Remineralization agents were applied to the specimens that were grouped as follows: Group 1, control; Group 2, fluoride varnish (FV); Group 3, P11-4; Group 4, laser; Group 5, laser + FV; and Group 6, laser + P11-4. The fluorescence level was determined with DiagnoDent. The enamel mineral density, area and volume, and caries lesion area and volume were determined with micro-computed tomography (µCT), surface features were evaluated using scanning electron microscopy (SEM), and elemental analysis was performed using energy dispersive x-ray spectroscopy (EDS) . For specimens treated only with self-assembling peptide P11-4, the caries lesion area (mm2) values were 38.19 and 21.62, and the caries lesion volume (mm3) values were 6.27 and 2.99, respectively for pre- and post-treatment. In combination usage of self-assembling peptide P11-4 and laser, the caries lesion area (mm2) values were 38.39 and 16.91, and the caries lesion volume (mm3) values were 11.15 and 3.64, respectively for pre- and post-treatment. In the application of the P11-4 alone and in combination with laser, there was a statistically significant decrease in DiagnoDent values, an increase in enamel volume(mm3),enamel area(mm2) and mineral density(g/cm3) values and a decrease in caries lesion volume(mm3) and area(mm2) obtained by µCT, and an increase in %Ca and %F values obtained by SEM/EDS analysis (p < 0.05). It was discovered that the samples treated with P11-4 had a considerably higher rise in the Ca/P ratio than the samples treated with FV (p < 0.05). The calcium content increased significantly more when P11-4 application was combined with laser irradiation (p < 0.05). The combined use of self-assembling peptide P11-4 and laser accelerated the remineralization process and increased the remineralization capacity. FV and P11-4, alone or in combination with laser, can be successfully used as remineralization agents in initial enamel caries.

Alkaline Phosphatase-Instructed Peptide Assemblies for Imaging and Therapeutic Applications.

Self-assembly, a powerful strategy for constructing highly stable and well-ordered supramolecular structures, widely exists in nature and in living systems. Peptides are frequently used as building blocks in the self-assembly process due to their advantageous characteristics, such as ease of synthesis, tunable mechanical stability, good biosafety, and biodegradability. Among the initiators for peptide self-assembly, enzymes are excellent candidates for guiding this process under mild reaction conditions. As a crucial and commonly used biomarker, alkaline phosphatase (ALP) cleaves phosphate groups, triggering a hydrophilicity-to-hydrophobicity transformation that induces peptide self-assembly. In recent years, ALP-instructed peptide self-assembly has made breakthroughs in biological imaging and therapy, inspiring the development of self-assembly biomaterials for diagnosis and therapeutics. In this review, we highlight the most recent advancements in ALP-instructed peptide assemblies and provide perspectives on their potential impact. Finally, we briefly discuss the ongoing challenges for future research in this field.

Dynamic control of His-hemin coordination and catalysis by reversible host–guest inclusion in peptide assemblies

Dynamic self-assembly has significant implications in the regulation of the enzyme activities. In this study, we present a histidine-based enzyme-mimicking catalyst, formed by the self-assembly of carefully-engineered FH-based short peptides with hemin, showcasing switchable catalytic activity of hemin due to externally induced reversible inclusion of a cucurbit[7]uril-peptide hybrid. 1H NMR, ITC and theoretical simulation are employed to examine the binding affinity between the guest and host components, and UV–vis spectra are used to investigate changes in the hemin coordination environment. The histidine segment of the short peptide can be partially shielded by the cucurbituril and released following addition of the azo compound, leading to a decrease and subsequent restoration of the histidine-hemin coordination affinity and hemin activity. The photoisomeriziable nature of the azo compound enabled the activation of FHH/hemin activity to be switched on and off by exposure to different wavelengths of light. During the operation, the Phe residue remained within the cucurbituril, allowing reversible inclusion and exposure of the histidine residues. The hemin stayed connected to FHH/cucurbit[7]uril hybrid, preventing the severe aggregation of hemin and irreversible deactivation. This work may provide insights into engineering the dynamic behaviors of the cofactor-dependent catalytic assemblies.

Rational design of self-assembling ultrashort peptides for the shape- and size-tunable synthesis of metal nanostructures.

Peptides have attracted great interest as platforms for the design of nanocomposite hydrogels due to their distinct bioactivity, biofunctionality and biocompatibility. Previously, we have reported on a family of peptides that self-assembled to form stabilised three-dimensional hydrogel networks, displaying potent antimicrobial activity. In this paper, we report on the use of these hydrogelator sequences and their analogues as stabilisers and growth controllers to synthesise anisotropic gold nanoparticles (AuNPs) of different sizes and shapes. In particular, hollow spherical nanoparticles were obtained for HG2.81-AuNPs, whereas hexagonal nanoparticles were observed for TOH_1N-AuNPs and PentaOH-AuNPs in their respective hydrogel networks. The PentaOH-AuNPs' hydrogel exhibited excellent results with high antimicrobial potency against Staphylococcus aureus and Pseudomonas aeruginosa ATCC 27853 and negligible cytotoxicity. On the other hand, TOH_1N-AuNPs showed no antibacterial activity and no cytotoxicity, demonstrating the versatility of these peptides. This work gives credence towards the development of these materials towards further applications such as in tissue culture technology and wound dressing materials.