Browse
Submit Data
Databases
API
Help

Dataset Information

20 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Enzyme-instructed hybrid nanogel/nanofiber oligopeptide hydrogel for localized protein delivery.

ABSTRACT: Enzyme-catalysis self-assembled oligopeptide hydrogel holds great interest in drug delivery, which has merits of biocompatibility, biodegradability and mild gelation conditions. However, its application for protein delivery is greatly limited by inevitable degradation of enzyme on the encapsulated proteins leading to loss of protein activity. Moreover, for the intracellularly acted proteins, cell membrane as a primary barrier hinders the transmembrane delivery of proteins. The internalized proteins also suffer from acidic and enzymatic degradation in endosomes and lysosomes. We herein develop a protease-manipulated hybrid nanogel/nanofiber hydrogel for localized delivery of intracellularly acted proteins. The embedded polymeric nanogels (CytoC/aNGs) preserve activity of cytochrome c (CytoC) that is an intracellular activator for cell apoptosis as a model protein against proteolysis, and do not affect the gelation properties of the protease-catalysis assembled hydrogels. The injectable hydrogel (CytoC/aNGs/Gel) serves as a reservoir to enhance intratumoral retention and realize sustainable release of CytoC/aNGs. The released CytoC/aNGs increase cellular uptake of CytoC and enhance its intracellular delivery to its target site, cytoplasm, resulting in favorable apoptosis-inducing and cytotoxic effects. We show that a single local administration of CytoC/aNGs/Gel efficiently inhibit the tumor growth in the breast tumor mouse model.

SUBMITTER: Jiang T

PROVIDER: S-EPMC8343108 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Localized Enzyme-Assisted Self-Assembly in the Presence of Hyaluronic Acid for Hybrid Supramolecular Hydrogel Coating.

Project description:Hydrogel coating is highly suitable in biomaterial design. It provides biocompatibility and avoids protein adsorption leading to inflammation and rejection of implants. Moreover, hydrogels can be loaded with biologically active compounds. In this field, hyaluronic acid has been largely studied as an additional component since this polysaccharide is naturally present in extracellular matrix. Strategies to direct hydrogelation processes exclusively from the surface using a fully biocompatible approach are rare. Herein we have applied the concept of localized enzyme-assisted self-assembly to direct supramolecular hydrogels in the presence of HA. Based on electronic and fluorescent confocal microscopy, rheological measurements and cell culture investigations, this work highlights the following aspects: (i) the possibility to control the thickness of peptide-based hydrogels at the micrometer scale (18-41 µm) through the proportion of HA (2, 5 or 10 mg/mL); (ii) the structure of the self-assembled peptide nanofibrous network is affected by the growing amount of HA which induces the collapse of nanofibers leading to large assembled microstructures underpinning the supramolecular hydrogel matrix; (iii) this changing internal architecture induces a decrease of the elastic modulus from 2 to 0.2 kPa when concentration of HA is increasing; (iv) concomitantly, the presence of HA in supramolecular hydrogel coatings is suitable for cell viability and adhesion of NIH 3T3 fibroblasts.

| S-EPMC8198348 | biostudies-literature

An injectable micelle-hydrogel hybrid for localized and prolonged drug delivery in the management of renal fibrosis.

Project description:Localized delivery, comparing to systemic drug administration, offers a unique alternative to enhance efficacy, lower dosage, and minimize systemic tissue toxicity by releasing therapeutics locally and specifically to the site of interests. Herein, a localized drug delivery platform ("plum‒pudding" structure) with controlled release and long-acting features is developed through an injectable hydrogel ("pudding") crosslinked via self-assembled triblock polymeric micelles ("plum") to help reduce renal interstitial fibrosis. This strategy achieves controlled and prolonged release of model therapeutics in the kidney for up to three weeks in mice. Following a single injection, local treatments containing either anti-inflammatory small molecule celastrol or anti-TGFβ antibody effectively minimize inflammation while alleviating fibrosis via inhibiting NF-κB signaling pathway or neutralizing TGF-β1 locally. Importantly, the micelle-hydrogel hybrid based localized therapy shows enhanced efficacy without local or systemic toxicity, which may represent a clinically relevant delivery platform in the management of renal interstitial fibrosis.

| S-EPMC7982499 | biostudies-literature

Research progress of self-assembled nanogel and hybrid hydrogel systems based on pullulan derivatives.

Project description:Polymer nano-sized hydrogels (nanogels) as drug delivery carriers have been investigated over the last few decades. Pullulan, a nontoxic and nonimmunogenic hydrophilic polysaccharide derived from fermentation of black yeast like Aureobasidium pullulans with great biocompatibility and biodegradability, is one of the most attractive carriers for drug delivery systems. In this review, we describe the preparation, characterization, and 'switch-on/off' mechanism of typical pullulan self-assembled nanogels (self-nanogels), and then introduce the development of hybrid hydrogels that are numerous resources applied for regenerative medicine. A major section is used for biomedical applications of different nanogel systems based on modified pullulan, which exert smart stimuli-responses at ambient conditions such as charge, pH, temperature, light, and redox. Pullulan self-nanogels have found increasingly extensive application in protein delivery, tissue engineering, vaccine development, cancer therapy, and biological imaging. Functional groups are incorporated into self-nanogels and contribute to expressing desirable results such as targeting and modified release. Various molecules, especially insoluble or unstable drugs and encapsulated proteins, present improved solubility and bioavailability as well as reduced side effects when incorporated into self-nanogels. Finally, the advantages and disadvantages of pullulan self-nanogels will be analyzed accordingly, and the development of pullulan nanogel systems will be reviewed.

| S-EPMC6058595 | biostudies-literature

The first CD73-instructed supramolecular hydrogel.

Project description:Enzymatic supramolecular hydrogelation is a simple, controllable, and novel strategy for preparation of soft colloidal materials, which allows the integration of self-assembly with enzyme associated biological processes. The development of more enzymes involve in hydrogelation is a subject of developing useful soft colloids. In this work, an ectoenzyme, CD73, was found to trigger the formation of nanofibers as matrices of hydrogels. CD73 is an important cell surface enzyme which converts extracellular adenosine monophosphate (AMP) to adenosine. It is broadly expressed in many cancer cells and participates in tumor growth. The successful application of CD73 in self-assembly and hydrogelation may provide new strategies for CD73-guided materials and therapies.

| S-EPMC4369398 | biostudies-literature

3D-Printable Hierarchical Nanogel-GelMA Composite Hydrogel System.

Project description:The strength of the extracellular matrix (ECM) is that it is hierarchical in terms of matrix built-up, matrix density and fiber structure, which allows for hormones, cytokines, and other small biomolecules to be stored within its network. The ECM-like hydrogels that are currently used do not possess this ability, and long-term storage, along with the need for free diffusion of small molecules, are generally incompatible requirements. Nanogels are able to fulfill the additional requirements upon successful integration. Herein, a stable hierarchical nanogel-gelatin methacryloyl (GelMA) composite hydrogel system is provided by covalently embedding nanogels inside the micropore network of GelMA hydrogel to allow a controlled local functionality that is not found in a homogenous GelMA hydrogel. Nanogels have emerged as a powerful tool in nanomedicine and are highly versatile, due to their simplicity of chemical control and biological compatibility. In this study, an N-isopropylacrylamide-based nanogel with primary amine groups on the surface was modified with methacryloyl groups to obtain a photo-cross-linking ability similar to GelMA. The nanogel-GelMA composite hydrogel was formed by mixing the GelMA and the photo-initiator within the nanogel solution through UV irradiation. The morphology of the composite hydrogel was observed by scanning electron microscopy, which clearly showed the nanogel wrapped within the GelMA network and covering the surface of the pore wall. A release experiment was conducted to prove covalent bonding and the stability of the nanogel inside the GelMA hydrogel. In addition, 3D printability studies showed that the nanogel-GelMA composite ink is printable. Therefore, the suggested stable hierarchical nanogel-GelMA composite hydrogel system has great potential to achieve the in situ delivery and controllable release of bioactive molecules in 3D cell culture systems.

| S-EPMC8348806 | biostudies-literature

Self-assembled pH-sensitive cholesteryl pullulan nanogel as a protein delivery vehicle.

Project description:A self-assembled nanogel, derived from an acid-labile cholesteryl-modified pullulan (acL-CHP), was prepared by grafting vinyl ether-cholesterol substituents onto a 100 kD pullulan main chain polymer backbone. Stable nanogels are formed by acL-CHP self-assemblies at neutral pH. The hydrodynamic radius of the nanogels, observed to be 26.5 ± 5.1 nm at pH 7.0, increased by ~135% upon acidification of the solution to pH 4.0. SEC analysis of the acL-CHP nanogel at pH 4.0 showed that the grafts were nearly 80% degraded after 24 h, whereas little or no degradation was observed over the same time period for a pH stable analog (acS-CHP) at pH 4.0 or the acL-CHP at pH 7.0. Complexation of BSA with the acL-CHP nanogel was observed at pH 7.0 with subsequent release of the protein upon acidification. These findings suggest that stimuli-responsive, self-assembled nanogels can release protein cargo in a manner that is controlled by the degradation rate of the cholesterol-pullulan grafting moiety.

| S-EPMC6900930 | biostudies-literature

Multifunctional Carrier Based on Halloysite/Laponite Hybrid Hydrogel for Kartogenin Delivery.

Project description:A novel carrier system based on halloysite nanotubes (HNT), for the potential intraarticular delivery of kartogenin (KGN) by means laponite (Lap) hydrogel (HNT/KGN/Lap), is developed. The drug was first loaded into HNT, and the hybrid composite obtained was used as filler for laponite hydrogel. Both the filler and the hydrogel were thoroughly investigated by several techniques and the hydrogel morphology was imaged by transmission electron microscopy. Furthermore, the gelating ability of laponite in the presence of the filler and the rheological properties of the hybrid hydrogel were also investigated. The kinetic release of kartogenin from HNT and HNT/Lap hybrid hydrogel was studied both in physiological conditions and in ex vivo synovial fluid. In the last case, the kinetic results highlighted that HNT carrier can effectively release KGN in a sustained manner for at least 38 days. Finally, a preliminary biological assays showed that the HNT/KGN/Lap hybrid hydrogel did not exhibit any cytotoxic effect.

| S-EPMC6466553 | biostudies-literature

Photo-triggerable Hydrogel-Nanoparticle Hybrid Scaffolds for Remotely Controlled Drug Delivery.

Project description:Remotely-triggerable drug delivery systems enable the user to adjust dosing regimens on-demand based on a patient's physiological response and clinical needs. However, currently reported systems are limited by the non-specific leakage of drugs in the absence of triggering and the lack of repeatability over multiple cycles of release. To this end, we have designed a unique hydrogel-nanoparticle hybrid scaffold that provides a chemically-defined, remotely-triggerable and on-demand release of small molecule drugs. Our hybrid platform consists of three distinct components: 1) a photo-triggerable chemical compound, which serves to release a covalently-bound drug upon photo-irradiation, 2) a nanoparticle, which serves to covalently bind the photo-triggerable compound, and 3) a polymeric hydrogel, which serves to hold the drug-conjugated nanoparticle. Upon photo-irradiation, the activation of the photo-triggerable compound is designed to initiate a series of intramolecular chemical rearrangements, which would cleave the covalently-bound drug and release it from the hydrogel. The combination of these distinct components in a single scaffold proved to be an effective drug delivery system, as demonstrated by the delivery of a model drug to a malignant cancer line. Our hybrid scaffold can be easily tuned for practically any biological application of interest, thus offering immense potential for clinical therapies.

| S-EPMC4285771 | biostudies-literature

Hybrid Nanoparticles and Composite Hydrogel Systems for Delivery of Peptide Antibiotics.

Project description:The growing number of drug-resistant pathogenic bacteria poses a global threat to human health. For this reason, the search for ways to enhance the antibacterial activity of existing antibiotics is now an urgent medical task. The aim of this study was to develop novel delivery systems for polymyxins to improve their antimicrobial properties against various infections. For this, hybrid core-shell nanoparticles, consisting of silver core and a poly(glutamic acid) shell capable of polymyxin binding, were developed and carefully investigated. Characterization of the hybrid nanoparticles revealed a hydrodynamic diameter of approximately 100 nm and a negative electrokinetic potential. The nanoparticles demonstrated a lack of cytotoxicity, a low uptake by macrophages, and their own antimicrobial activity. Drug loading and loading efficacy were determined for both polymyxin B and E, and the maximal loaded value with an appropriate size of the delivery systems was 450 µg/mg of nanoparticles. Composite materials based on agarose hydrogel were prepared, containing both the loaded hybrid systems and free antibiotics. The features of polymyxin release from the hybrid nanoparticles and the composite materials were studied, and the mechanisms of release were analyzed using different theoretical models. The antibacterial activity against Pseudomonas aeruginosa was evaluated for both the polymyxin hybrid and the composite delivery systems. All tested samples inhibited bacterial growth. The minimal inhibitory concentrations of the polymyxin B hybrid delivery system demonstrated a synergistic effect when compared with either the antibiotic or the silver nanoparticles alone.

| S-EPMC8911036 | biostudies-literature

β-Galactosidase-instructed formation of molecular nanofibers and a hydrogel.

Project description:Here we report the first example of using β-galactosidase to trigger the formation of cell compatible, supramolecular nanofibers, which ultimately may lead to a new approach for the development of soft nanotechnology.

| S-EPMC3235787 | 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