Browse
Submit Data
Databases
API
Help

Dataset Information

8 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A supramolecular protein chaperone for vaccine delivery.

ABSTRACT: Rationale: Nanomaterials capable of specifically interacting with proteins are very important for protein storage and vaccine delivery. Supramolecular hydrogels based on peptides have emerged as promising vaccine adjuvants because of their good compatibility, ease of antigen incorporation and display, and efficiency in activating immune responses. Methods: We synthesized a self-assembling peptide (Fbp-G^DF^DF^DY^DK(γE)₂-NH₂, Comp. 1 ) serving as a supramolecular protein chaperone for protein antigen delivery. The gelation was triggered by simply mixing Comp. 1 and proteins. The vaccine adjuvant potential of Comp. 1 was demonstrated by using two protein antigens, ovalbumin (OVA) and hepatitis B surface antigen (HBsAg). Results: The peptide derivative Comp. 1 exhibited high protein binding capacity. Upon contacting proteins, Comp. 1 rapidly formed coassembled nanofibers/hydrogels with the proteins, which greatly delayed the release of protein antigens. Our supramolecular protein chaperone significantly stimulated specific antibody titers by assisting protein delivery to antigen-presenting cells, promoting dendritic cell (DC) maturation, prolonging antigen accumulation and retention in the lymph nodes, and eliciting the secretion of cytokines. Most importantly, our supramolecular protein chaperone strongly stimulated the cellular immune response and significantly retarded tumor growth. Conclusion: Our study demonstrated the great potential of the supramolecular protein chaperone in protein storage and delivery, vaccine production and tumor immunotherapy.

SUBMITTER: Wang Z

PROVIDER: S-EPMC6929975 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Supramolecular Hydrogels for Protein Delivery in Tissue Engineering.

Project description:Therapeutic proteins, such as growth factors (GFs), have been used in tissue engineering (TE) approaches for their ability to provide signals to cells and orchestrate the formation of functional tissue. However, to be effective and minimize off-target effects, GFs should be delivered at the target site with temporal control. In addition, protein drugs are typically sensitive water soluble macromolecules with delicate structure. As such, hydrogels, containing large amounts of water, provide a compatible environment for the direct incorporation of proteins within the hydrogel network, while their release rate can be tuned by engineering the network chemistry and density. Being formed by transient crosslinks, afforded by non-covalent interactions, supramolecular hydrogels offer important advantages for protein delivery applications. This review describes various types of supramolecular hydrogels using a repertoire of diverse building blocks, their use for protein delivery and their further application in TE contexts. By reviewing the recent literature on this topic, the merits of supramolecular hydrogels are highlighted as well as their limitations, with high expectations for new advances they will provide for TE in the near future.

| S-EPMC7914635 | biostudies-literature

Protein delivery into cells using inorganic nanoparticle-protein supramolecular assemblies.

Project description:The delivery of proteins into cells is a potential game changer for a wide array of therapeutic purposes, including cancer therapy, immunomodulation and treatment of inherited diseases. In this review, we present recently developed nanoassemblies for protein delivery that utilize strategies that range from direct assembly, encapsulation and composite formation. We will discuss factors that affect the efficacy of nanoassemblies for delivery from the perspective of both nanoparticles and proteins. Challenges in the field, particularly achieving effective cytosolar protein delivery through endosomal escape or evasion are discussed.

| S-EPMC5962404 | biostudies-literature

Co-assembled Supramolecular Nanofibers With Tunable Surface Properties for Efficient Vaccine Delivery.

Project description:The utilization of nanotechnology to deliver vaccines and modulate immunity has shown great potential in cancer therapy. Peptide-based supramolecular hydrogels as novel vaccine adjuvants have been found to effectively improve the immune response and tumor curative effect. In this study, we designed a set of reduction-responsive self-assembled peptide precursors (Fbp-GDFDFDYD(E, S, or K)-ss-ERGD), which can be reduced by glutathione (GSH) into Fbp-GDFDFDYD(E, S or K)-SH for forming of hydrogel with different surface properties (E-gel, S-gel, and K-gel, respectively). Using the same method, co-assembled hydrogel vaccines (E-vac, S-vac, and K-vac, respectively) can also be prepared by mixing different precursors with antigens before GSH reduction. Through TEM observation of the nanostructure, we found that all the co-assembled hydrogels, especially K-vac, possessed much denser and more unified nanofiber networks as compared with antigen-free hydrogels, which were very suitable for antigen storage and vaccine delivery. Although the three peptides adopted similar β-sheet secondary structures, the mechanical properties of their resulted co-assembled hydrogel vaccines were obviously different. Compared to E-vac, S-vac had a much weaker mechanical property, while K-vac had a much higher. In vivo experiments, co-assembled hydrogel vaccines, especially K-vac, also promoted antibody production and anti-tumor immune responses more significantly than the other two vaccines. Our results demonstrated that co-assembled hydrogels formed by peptides and antigens co-assembly could act as effective vaccine delivery systems for boosting antibody production, and different immune effects can be acquired by tuning the surface properties of the involved self-assembling peptides.

| S-EPMC7396696 | biostudies-literature

A self-adjuvanting supramolecular vaccine carrying a folded protein antigen.

Project description:This work illustrates a strategy for the design of molecularly defined immunotherapies, using a blend of supramolecular peptide self-assembly and active site-directed protein capture.

| S-EPMC3817840 | biostudies-literature

Short oligoalanine helical peptides for supramolecular nanopore assembly and protein cytosolic delivery.

Project description:In this work we report a rational design strategy for the identification of new peptide prototypes for the non-disruptive supramolecular permeation of membranes and the transport of different macromolecular giant cargos. The approach targets a maximal enhancement of helicity in the presence of membranes with sequences bearing the minimal number of cationic and hydrophobic moieties. The here reported folding enhancement in membranes allowed the selective non-lytic translocation of different macromolecular cargos including giant proteins. The transport of different high molecular weight polymers and functional proteins was demonstrated in vesicles and in cells with excellent efficiency and optimal viability. As a proof of concept, functional monoclonal antibodies were transported for the first time into different cell lines and cornea tissues by exploiting the helical control of a short peptide sequence. This work introduces a rational design strategy that can be employed to minimize the number of charges and hydrophobic residues of short peptide carriers to achieve non-destructive transient membrane permeation and transport of different macromolecules.

| S-EPMC8341679 | biostudies-literature

Chaperone-like chiral cages for catalyzing enantio-selective supramolecular polymerization.

Project description:Cage catalysis has emerged as an important approach for mimicking enzymatic reactions by increasing the reaction rate and/or product selectivity of various types of covalent reactions. Here, we extend the catalytic application of cage compounds to the field of non-covalent molecular assembly. Acid-stable chiral imine cages are found to catalyze the supramolecular polymerization of porphyrins with an accelerated assembling rate and increased product enantioselectivity. Because the imine cages have a stronger interaction with porphyrin monomers and a weaker interaction with porphyrin assemblies, they can fully automatically detach from the assembled products without being consumed during the catalytic process. We reveal the kinetics of the auto-detachment of cages and the chirality growth of the assemblies using spectroscopic characterization studies. We find that the passivation groups attached to the cages are important for maintaining the structural stability of the cages during catalyzed assembly, and that the steric geometries of the cages can profoundly affect the efficiency of chiral regulation. This strategy demonstrates a new type of catalytic application of cage compounds in the field of molecular assembly, and paves the way to controlling supramolecular polymerization through a catalytic pathway.

| S-EPMC6910136 | biostudies-literature

Injectable Supramolecular Hydrogel/Microgel Composites for Therapeutic Delivery.

Project description:Shear-thinning hydrogels are useful for biomedical applications, from 3D bioprinting to injectable biomaterials. Although they have the appropriate properties for injection, it may be advantageous to decouple injectability from the controlled release of encapsulated therapeutics. Toward this, composites of hydrogels and encapsulated microgels are introduced with microgels that are fabricated via microfluidics. The microgel cross-linker controls degradation and entrapped molecule release, and the concentration of microgels alters composite hydrogel rheological properties. For the treatment of myocardial infarction (MI), interleukin-10 (IL-10) is encapsulated in microgels and released from composites. In a rat model of MI, composites with IL-10 reduce macrophage density after 1 week and improve scar thickness, ejection fraction, cardiac output, and the size of vascular structures after 4 weeks when compared to saline injection. Improvements are also observed with the composite without IL-10 over saline, emphasizing the role of injectable hydrogels alone on tissue repair.

| S-EPMC6396315 | biostudies-literature

Supramolecular caging for cytosolic delivery of anionic probes.

Project description:The cytosolic delivery of hydrophilic, anionic molecular probes and therapeutics is a major challenge in chemical biology and medicine. Herein, we describe the design and synthesis of peptide-cage hybrids that allow an efficient supramolecular binding, cell membrane translocation and cytosolic delivery of a number of anionic dyes, including pyranine, carboxyfluorescein and several sulfonate-containing Alexa dyes. This supramolecular caging strategy is successful in different cell lines, and the dynamic carrier mechanism has been validated by U-tube experiments. The high efficiency of the reported approach allowed intracellular pH tracking by exploiting the ratiometric excitation of the pyranine fluorescent probe.

| S-EPMC7017865 | biostudies-literature

Tumor Microenvironment-Responsive Peptide-Based Supramolecular Drug Delivery System.

Project description:Physical and biochemical differences between tumor tissues and normal tissues provide promising triggering factors that can be utilized to engineer stimuli-responsive drug delivery platforms for cancer treatment. Rationally designed peptide-based supramolecular architectures can perform structural conversion by responding to the tumor microenvironment and achieve the controlled release of antitumor drugs. This mini review summarizes recent approaches for designing internal trigger-responsive drug delivery platforms using peptide-based materials. Peptide assemblies that exhibit a stimuli-responsive structural conversion upon acidic pH, high temperature, high oxidative potential, and the overexpressed proteins in tumor tissues are emphatically introduced. We also discuss the challenges of current peptide-based supramolecular delivery platforms against cancer.

| S-EPMC7388741 | biostudies-literature

Enhanced Delivery of Neuroactive Drugs via Nasal Delivery with a Self-Healing Supramolecular Gel.

Project description:This paper reports the use of a self-assembling hydrogel as a delivery vehicle for the Parkinson's disease drug l-DOPA. Based on a two-component combination of an l-glutamine amide derivative and benzaldehyde, this gel has very soft rheological properties and self-healing characteristics. It is demonstrated that the gel can be formulated to encapsulate l-DOPA. These drug-loaded gels are characterized, and rapid release of the drug is obtained from the gel network. This drug-loaded hydrogel has appropriate rheological characteristics to be amenable for injection. This system is therefore tested as a vehicle for nasal delivery of neurologically-active drugs-a drug delivery strategy that can potentially avoid first pass liver metabolism and bypass the blood-brain barrier, hence enhancing brain uptake. In vitro tests indicate that the gel has biocompatibility with respect to nasal epithelial cells. Furthermore, animal studies demonstrate that the nasal delivery of a gel loaded with 3 H-labeled l-DOPA out-performed a simple intranasal l-DOPA solution. This is attributed to longer residence times of the gel in the nasal cavity resulting in increased blood and brain concentrations. It is demonstrated that the likely routes of brain penetration of intranasally-delivered l-DOPA gel involve the trigeminal and olfactory nerves connecting to other brain regions.

| S-EPMC8292877 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data