Browse
Submit Data
Databases
API
Help

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Injectable Peptide Hydrogel Enables Integrated Tandem Enzymes' Superactivity for Cancer Therapy.

ABSTRACT: Elevation of the levels of reactive oxygen species and other toxic radicals is an emerging strategy to treat certain cancers by modulating the redox status of cancer cells. The biocatalytic upregulation of singlet oxygen by neutrophilic leukocytes should utilize robust enzymes and design carriers with protective microenvironment. Here, we utilize GOx-CPO as integrated tandem enzymes to in situ generate singlet oxygen, which could be not only for oxidative cross-linking of injectable hydrogel carriers but also for continuous tumor treatment by adjustable bioconversion of blood oxygen, glucose, and chloride ion. The tandem enzymes self-restrained within peptide hydrogel exhibited superactivity for upregulating singlet oxygen relative to free enzymes, which also avoids the diffusion of enzymes from tumor. This work will not only deepen the study of enzymes in biocatalysis but also offer an enzyme therapeutic modality for treating cancers.

SUBMITTER: Wei Q

PROVIDER: S-EPMC6438909 | biostudies-other | 2019 Apr

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Publications

Injectable Peptide Hydrogel Enables Integrated Tandem Enzymes' Superactivity for Cancer Therapy.

Wei Qingcong Q Jiang Shan S Zhu Rongrong R Wang Xia X Wang Shilong S Wang Qigang Q

iScience 20190315

Elevation of the levels of reactive oxygen species and other toxic radicals is an emerging strategy to treat certain cancers by modulating the redox status of cancer cells. The biocatalytic upregulation of singlet oxygen by neutrophilic leukocytes should utilize robust enzymes and design carriers with protective microenvironment. Here, we utilize GOx-CPO as integrated tandem enzymes to in situ generate singlet oxygen, which could be not only for oxidative cross-linking of injectable hydrogel car ...[more]

PMID: 30921734

Similar Datasets

Injectable solid hydrogel: mechanism of shear-thinning and immediate recovery of injectable ?-hairpin peptide hydrogels.

Project description:?-Hairpin peptide-based hydrogels are a class of injectable hydrogel solids with significant potential use in injectable therapies. ?-hairpin peptide hydrogels can be injected as preformed solids, because the solid gel can shear-thin and consequently flow under a proper shear stress but immediately recover back into a solid on removal of the stress. In this work, hydrogel behavior during and after flow was studied in order to facilitate fundamental understanding of how the gels flow during shear-thinning and how they quickly recover mechanically and morphologically relative to their original, pre-flow properties. While all studied ?-hairpin hydrogels shear-thin and recover, the duration of shear and the strain rate affected both the gel stiffness immediately recovered after flow and the ultimate stiffness obtained after complete rehealing of the gel. Results of structural analysis during flow were related to bulk rheological behavior and indicated gel network fracture into large (>200 nm) hydrogel domains during flow. After cessation of flow the large hydrogel domains are immediately percolated which immediately reforms the solid hydrogel. The underlying mechanisms of the gel shear-thinning and healing processes are discussed relative to other shear-responsive networks like colloidal gels and micellar solutions.

| S-EPMC3091287 | biostudies-literature

Injectable Hydrogel for Synergetic Low Dose Radiotherapy, Chemodynamic Therapy and Photothermal Therapy.

Project description:Higher doses of radiotherapy (RT) are associated with resistance induction, therefore highly selective and controllable radiosensitizers are urgently needed. To address this issue, we developed a FeGA-based injectable hydrogel system (FH) that can be used in combination with low-dose radiation. Our FH can deliver FeGA directly to the tumor site via intratumoral injection, where it is a reservoir-based system to conserve FeGA. The photothermal properties of FeGA steadily dissolve FH under laser irradiation, and, simultaneously, FeGA reacts with a large amount of H2O2 in the cell to produce OH (Fenton reaction) which is highly toxic to mitochondria, rendering the cell inactive and reducing radiotherapy resistance. In vivo and in vitro studies suggest that combining the FH and NIR irradiation with RT (2Gy) can significantly reduce tumor proliferation without side effects such as inflammation. To conclude, this is the first study to achieve combined chemodynamic therapy (CDT) and photothermal therapy (PTT) in situ treatment, and the best therapeutic effect can be obtained with a low-dose radiation combination, thus expanding the prospects of FeGA-based tumor therapy.

| S-EPMC8645961 | biostudies-literature

Injectable Glycol Chitosan Hydrogel Containing Folic Acid-Functionalized Cyclodextrin-Paclitaxel Complex for Breast Cancer Therapy.

Project description:We prepared a drug carrier which consisted of injectable methacrylated glycol chitosan (MGC) hydrogel, and a conjugate of 6-monodeoxy-6-monoamino-β-cyclodextrin⋅hydrochloride (6-NH2-β-CD⋅HCl), polyethylene glycol (PEG), and folic acid (FA) for the local delivery and improved cellular uptake of paclitaxel (PTX) (MGC/CDPF-ic-PTX). CDPF refers to a conjugate of 6-NH2-β-CD⋅HCl, PEG, and FA. The anti-cancer effect was investigated using a xenograft mouse model. As controls, the animal study on MGC/PTX and MGC/CD-ic-PTX was performed. The swelling ratio of all samples was analyzed for 7 days, and it showed a gradual increase for 3 days and a maintained state afterward. From the release result, the MGC-based samples have an initial burst for 1 day and a sustained release for 7 days. Results of cytotoxicity and animal study showed the biocompatibility and superior anti-cancer effect of MGC/CDPF-ic-PTX against breast cancer. Furthermore, histological results showed the anti-cancer capacity of MGC/CDPF-ic-PTX against breast cancer. These findings suggest that MGC/CDPF-ic-PTX has clinical potential for breast cancer therapy.

| S-EPMC7910883 | biostudies-literature

Injectable Alginate-Peptide Composite Hydrogel as a Scaffold for Bone Tissue Regeneration.

Project description:The high demand for tissue engineering scaffolds capable of inducing bone regeneration using minimally invasive techniques prompts the need for the development of new biomaterials. Herein, we investigate the ability of Alginate incorporated with the fluorenylmethoxycarbonyl-diphenylalanine (FmocFF) peptide composite hydrogel to serve as a potential biomaterial for bone regeneration. We demonstrate that the incorporation of the self-assembling peptide, FmocFF, in sodium alginate leads to the production of a rigid, yet injectable, hydrogel without the addition of cross-linking agents. Scanning electron microscopy reveals a nanofibrous structure which mimics the natural bone extracellular matrix. The formed composite hydrogel exhibits thixotropic behavior and a high storage modulus of approximately 10 kPA, as observed in rheological measurements. The in vitro biocompatibility tests carried out with MC3T3-E1 preosteoblast cells demonstrate good cell viability and adhesion to the hydrogel fibers. This composite scaffold can induce osteogenic differentiation and facilitate calcium mineralization, as shown by Alizarin red staining, alkaline phosphatase activity and RT-PCR analysis. The high biocompatibility, excellent mechanical properties and similarity to the native extracellular matrix suggest the utilization of this hydrogel as a temporary three-dimensional cellular microenvironment promoting bone regeneration.

| S-EPMC6523611 | biostudies-literature

Injectable bio-responsive hydrogel for therapy of inflammation related eyelid diseases.

Project description:Eyelid plays a vital role in protecting the eye from injury or infection. Inflammation related eyelid diseases, such as blepharitis, are the most common ocular disorders that affect human's vision and quality of life. Due to the physiological barriers and anatomical structures of the eye, the bioavailability of topical administrated therapeutics is typically less than 5%. Herein, we developed a bio-responsive hydrogel drug delivery system using a generally recognized as safe compound, triglycerol monostearate (TG-18), for in-situ eyelid injection with sustained therapeutics release. In vitro, drug release and disassembly time of Rosiglitazone loaded hydrogel (Rosi-hydrogel) were estimated in the presence or absence of MMP-9, respectively. Moreover, the disassembly of TG-18 hydrogel was evaluated with 9-month-old and 12-month-old mice in vivo. Owing to the bio-responsive nature of Rosi-hydrogel, the on-demand Rosiglitazone release is achieved in response to local enzymes. These findings are proved by further evaluation in the age-related meibomian gland dysfunction mice model, and the bio-responsive hydrogel is used as an in-situ injection to treat eyelid diseases. Taken together, the in-situ eyelid injection with sustained drug release opens a window for the therapy of inflammation related eyelid diseases.

| S-EPMC7960684 | biostudies-literature

Injectable anti-inflammatory supramolecular nanofiber hydrogel to promote ranibizumab therapy in age-related macular degeneration treatment

Project description:The exact pathogenesis of age-related macular degeneration (AMD) leading to visual impairment and severe vision loss is still unclear, and the currently available treatments are often unsatisfactory. Previous studies have demonstrated both oxidative stress-induced damage to the retinal pigment epithelium (RPE) and inflammation are involved in AMD. Although anti-vascular endothelial growth factor (VEGF) therapy can impair the growth of new blood vessels, serious side effects were found with repeated monthly intravitreal injections. Here, an injectable hydrogel based on an anti-inflammatory betamethasone phosphate (BetP) drug (BetP-Gel) was designed to enable long-term efficient release of ranibizumab (RZB) to attenuate choroidal neovascularization (CNV), reduce vascular leakage and inhibit vascular proliferation in the retina, which significantly increased the effective treatment time of ranibizumab compared with that in clinical practice. In particular, experimental data with in vitro and in vivo models revealed that BetP-Gel itself had a strong ability to scavenge intracellular reactive oxygen species (ROS) and reduce tumour necrosis factor-α (TNF-α) as well as interleukin (IL-1β, IL-6, IL-8, and IL-18) inflammatory cytokines, inhibiting ROS- and inflammation-induced retinal damage. Altogether, the carrier-free system (RZB@BetP-Gel) could serve as a novel antioxidant, anti-inflammatory and anti-neovascularization agent for the treatment of AMD.

2024-01-28 | GSE165702 | GEO

"A novel highly stable and injectable hydrogel based on a conformationally restricted ultrashort peptide".

Project description:Nanostructures including hydrogels based on peptides containing non protein amino acids are being considered as platform for drug delivery because of their inherent biocompatibility and additional proteolytic stability. Here we describe instantaneous self-assembly of a conformationally restricted dipeptide, Leu?Phe, containing an ?,?-dehydrophenylalanine residue into a highly stable and mechanically strong hydrogel, under mild physiological aqueous conditions. The gel successfully entrapped several hydrophobic and hydrophilic drug molecules and released them in a controlled manner. Leu?Phe was highly biocompatible and easily injectable. Administration of an antineoplastic drug entrapped in the gel in tumor bearing mice significantly controlled growth of tumors. These characteristics make Leu?Phe an attractive candidate for further development as a delivery platform for various biomedical applications.

| S-EPMC4979021 | biostudies-other

Injectable Hydrogel System for Camptothecin Initiated Nanocatalytic Tumor Therapy With High Performance.

Project description:Single photothermal therapy (PTT) has many limitations in tumor treatments. Multifunctional nanomaterials can cooperate with PTT to achieve profound tumor killing performance. Herein, we encapsulated chemotherapeutic drug camptothecin (CPT) and pyrite (FeS2) with dual enzyme activity (glutathione oxidase (GSH-OXD) and peroxidase (POD) activities) into an injectable hydrogel to form a CFH system, which can improve the level of intratumoral oxidative stress, and simultaneously realize FeS2-mediated PTT and nanozymes catalytic treatment. After laser irradiation, the hydrogel gradually heats up and softens under the photothermal agent FeS2. The CPT then released from CFH to tumor microenvironment (TME), thereby enhancing the H2O2 level. As a result, FeS2 can catalyze H2O2 to produce ·OH, and cooperate with high temperature to achieve high-efficiency tumor therapy. It is worth noting that FeS2 can also deplete excess glutathione (GSH) in the cellular level, further amplifying oxidative stress. Both in vivo and in vitro experiments show that our CFH exhibits good tumor-specific cytotoxicity. The CFH we developed provides new insights for tumor treatment.

| S-EPMC9280668 | biostudies-literature

The effect of protein structure on their controlled release from an injectable peptide hydrogel.

Project description:Hydrogel materials are promising vehicles for the delivery of protein therapeutics. Proteins can impart physical interactions, both steric and electrostatic in nature, that influence their release from a given gel network. Here, model proteins of varying hydrodynamic diameter and charge are directly encapsulated and their release studied from electropositive fibrillar hydrogels prepared from the self-assembling peptide, MAX8. Hydrogelation of MAX8 can be triggered in the presence of proteins for their direct encapsulation with neither effect on protein structure nor the hydrogel's mechanical properties. Bulk release of the encapsulated proteins from the hydrogels was assessed for a month time period at 37 °C before and after syringe delivery of the loaded gels to determine the influence of the protein structure on release. Release of positively charged and neutral proteins was largely governed by the sterics imposed by the network. Conversely, negatively charged proteins interacted strongly with the positively charged fibrillar network, greatly restricting their release to <10% of the initial protein load. Partition and retention studies indicated that electrostatic interactions dictate the amount of protein available for release. Importantly, when protein encapsulated gels were delivered via syringe, the release profiles of the macromolecules show the similar trends as those observed for non-sheared gels. This study demonstrates that proteins can be directly encapsulated in self assembled MAX8 hydrogels, which can then be syringe delivered to a site where subsequent release is controlled by protein structure.

| S-EPMC2976777 | biostudies-literature

Injectable peptide hydrogel as intraperitoneal triptolide depot for the treatment of orthotopic hepatocellular carcinoma.

Project description:Chemotherapy is among the limited choices approved for the treatment of hepatocellular carcinoma (HCC) at intermediate and advanced stages. Preferential and prolonged drug exposure in diseased sites is required to maximize the therapeutic index of the drug. Here, we report an injectable supramolecular peptide hydrogel as an intraperitoneal depot for localized and sustained release of triptolide for the treatment of orthotopic HCC. We chose peptide amphiphile C16-GNNQQNYKD-OH-based nanofibers as gelators and carriers for triptolide. Sustained triptolide release from the hydrogel was achieved over 14 days in vitro, with higher accumulation in and cytotoxicity against human HCC Bel-7402 in comparison with L-02 fetal hepatocytes. After intraperitoneal injection, the hydrogel showed prolonged retention over 13 days and preferential accumulation in the liver, realizing HCC growth inhibition by 99.7 ± 0.1% and animal median survival extension from 19 to 43 days, without causing noticeable pathological changes in the major organs. These results demonstrate that injectable peptide hydrogel can be a potential carrier for localized chemotherapy of HCC.

| S-EPMC6804453 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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