Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Control of Intra- versus Extracellular Bioorthogonal Catalysis Using Surface-Engineered Nanozymes.

ABSTRACT: Bioorthogonal transformation of prodrugs and profluorophores using transition metal catalysts (TMCs) offers a promising strategy for therapeutic and imaging applications. Here, we report the surface engineering of nanoparticles to specifically localize gold nanoparticles (AuNPs) with encapsulated TMCs (nanozymes) to either the inside or outside of cells. The ability to control nanozyme localization and hence activity was demonstrated by the activation of pro-fluorophores and prodrugs intra- and extracellularly, establishing the potential of engineered nanozyme platforms for both diagnostic and therapeutic purposes.

SUBMITTER: Das R

PROVIDER: S-EPMC6779054 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Control of Intra- versus Extracellular Bioorthogonal Catalysis Using Surface-Engineered Nanozymes.

Das Riddha R Landis Ryan F RF Tonga Gulen Yesilbag GY Cao-Milán Roberto R Luther David C DC Rotello Vincent M VM

ACS nano 20181210 1

Bioorthogonal transformation of prodrugs and profluorophores using transition metal catalysts (TMCs) offers a promising strategy for therapeutic and imaging applications. Here, we report the surface engineering of nanoparticles to specifically localize gold nanoparticles (AuNPs) with encapsulated TMCs (nanozymes) to either the inside or outside of cells. The ability to control nanozyme localization and hence activity was demonstrated by the activation of pro-fluorophores and prodrugs intra- and ...[more]

PMID: 30516966

Similar Datasets

Protection and Isolation of Bioorthogonal Metal Catalysts by Using Monolayer-Coated Nanozymes.

Project description:We demonstrate here the protection of biorthogonal transition metal catalysts (TMCs) in biological environments by using self-assembled monolayers on gold nanoparticles (AuNPs). Encapsulation of TMCs in this hydrophobic environment preserves catalytic activity in presence of pH conditions and complex biological media that would deactivate free catalyst. Significantly, the protection affords by these nanozymes extends to isolation of the catalyst active site, as demonstrated by the independence of rate over a wide pH range, in strong contrast to the behavior of the free catalyst.

| S-EPMC7541601 | biostudies-literature

Macrophage-Encapsulated Bioorthogonal Nanozymes for Targeting Cancer Cells.

Project description:Macrophages migrate to tumor sites by following chemoattractant gradients secreted by tumor cells, providing a truly active targeting strategy for cancer therapy. However, macrophage-based delivery faces challenges of cargo loading, control of release, and effects of the payload on the macrophage vehicle. We present a strategy that employs bioorthogonal "nanozymes" featuring transition metal catalysts (TMCs) to provide intracellular "factories" for the conversion of prodyes and prodrugs into imaging agents and chemotherapeutics. These nanozymes solubilize and stabilize the TMCs by embedding them into self-assembled monolayer coating gold nanoparticles. Nanozymes delivered into macrophages were intracellularly localized and retained activity even after prolonged (72 h) incubation. Significantly, nanozyme-loaded macrophages maintained their inherent migratory ability toward tumor cell chemoattractants, efficiently killing cancer cells in cocultures. This work establishes the potential of nanozyme-loaded macrophages for tumor site activation of prodrugs, providing readily tunable dosages and delivery rates while minimizing off-target toxicity of chemotherapeutics.

| S-EPMC9327086 | biostudies-literature

Charge-Switchable Nanozymes for Bioorthogonal Imaging of Biofilm-Associated Infections.

Project description:Early detection of biofilms is crucial for limiting infection-based damage. Imaging these biofilms is challenging: conventional imaging agents are unable to penetrate the dense matrix of the biofilm, and many imaging agents are susceptible to false positive/negative responses due to phenotypical mutations of the constituent microbes. We report the creation of pH-responsive nanoparticles with embedded transition metal catalysts (nanozymes) that effectively target the acidic microenvironment of biofilms. These pH-switchable nanozymes generate imaging agents through bioorthogonal activation of profluorophores inside biofilms. The specificity of these nanozymes for imaging biofilms in complex biosystems was demonstrated using coculture experiments.

| S-EPMC5846330 | biostudies-literature

Intracellular Activation of Bioorthogonal Nanozymes through Endosomal Proteolysis of the Protein Corona.

Project description:Bioorthogonal activation of prodrugs provides a strategy for on-demand on-site production of therapeutics. Intracellular activation provides a strategy to localize therapeutics, potentially minimizing off-target effects. To this end, nanoparticles embedded with transition metal catalysts (nanozymes) were engineered to generate either "hard" irreversible or "soft" reversible coronas in serum. The hard corona induced nanozyme aggregation, effectively inhibiting nanozyme activity, whereas only modest loss of activity was observed with the nonaggregating soft corona nanozymes. In both cases complete activity was restored by treatment with proteases. Intracellular activity mirrored this reactivation: endogenous proteases in the endosome provided intracellular activation of both nanozymes. The role of intracellular proteases in nanozyme reactivation was verified through treatment of the cells with protease inhibitors, which prevented reactivation. This study demonstrates the use of intracellular proteolysis as a strategy for localization of therapeutic generation to within cells.

| S-EPMC8297610 | biostudies-literature

Supramolecular regulation of bioorthogonal catalysis in cells using nanoparticle-embedded transition metal catalysts.

Project description:Bioorthogonal catalysis broadens the functional possibilities of intracellular chemistry. Effective delivery and regulation of synthetic catalytic systems in cells are challenging due to the complex intracellular environment and catalyst instability. Here, we report the fabrication of protein-sized bioorthogonal nanozymes through the encapsulation of hydrophobic transition metal catalysts into the monolayer of water-soluble gold nanoparticles. The activity of these catalysts can be reversibly controlled by binding a supramolecular cucurbit[7]uril 'gate-keeper' onto the monolayer surface, providing a biomimetic control mechanism that mimics the allosteric regulation of enzymes. The potential of this gated nanozyme for use in imaging and therapeutic applications was demonstrated through triggered cleavage of allylcarbamates for pro-fluorophore activation and propargyl groups for prodrug activation inside living cells.

| S-EPMC5697749 | biostudies-literature

Photoredox Heterobimetallic Dual Catalysis Using Engineered Covalent Organic Frameworks.

Project description:The functionalization of an imine-based layered covalent organic framework (COF), containing phenanthroline units as ligands, has allowed the obtention of a heterobimetallated material. Photoactive Ir and Ni fragments were immobilized within the porous structure of the COF, enabling heterogeneous light-mediated Csp3-Csp2 cross-couplings. As radical precursors, potassium benzyl- and alkoxy-trifluoroborates, organic silicates, and proline derivatives were employed, which brings out the good versatility of Ir,Ni@Phen-COF. Moreover, in all the studied cases, an enhanced activity and stability have been observed in comparison with analogous homogenous systems.

| S-EPMC8650013 | biostudies-literature

Surface modifications created by using engineered hydrophobins.

Project description:Hydrophobins are small (ca. 100 amino acids) secreted fungal proteins that are characterized by the presence of eight conserved cysteine residues and by a typical hydropathy pattern. Class I hydrophobins self-assemble at hydrophilic-hydrophobic interfaces into highly insoluble amphipathic membranes, thereby changing the nature of surfaces. Hydrophobic surfaces become hydrophilic, while hydrophilic surfaces become hydrophobic. To see whether surface properties of assembled hydrophobins can be changed, 25 N-terminal residues of the mature SC3 hydrophobin were deleted (TrSC3). In addition, the cell-binding domain of fibronectin (RGD) was fused to the N terminus of mature SC3 (RGD-SC3) and TrSC3 (RGD-TrSC3). Self-assembly and surface activity were not affected by these modifications. However, physiochemical properties at the hydrophilic side of the assembled hydrophobin did change. This was demonstrated by a change in wettability and by enhanced growth of fibroblasts on Teflon-coated with RGD-SC3, TrSC3, or RGD-TrSC3 compared to bare Teflon or Teflon coated with SC3. Thus, engineered hydrophobins can be used to functionalize surfaces.

| S-EPMC123772 | biostudies-literature

Intra-articular hip injection using anatomic surface landmarks.

Project description:Intra-articular hip injection is a frequently used technique for diagnostic and therapeutic purposes and is gaining more importance for the early diagnosis of hip disease. It is commonly performed with imaging guidance such as ultrasonographic or fluoroscopic control. We describe our technique of injection of the hip using relative distances from anatomic surface landmarks, with the needle insertion point at the site of the proximal anterolateral portal for hip arthroscopy, with a posterior direction of 30° and targeted toward a junctional point between 2 perpendicular lines, 1 distal from the anterior superior iliac spine and the second anterior from the tip of the greater trochanter. This technique can be used without imaging guidance in the outpatient clinic. Moreover, it minimizes the need for radiographic exposure for more critical injections, such as the injection of contrast material before conducting magnetic resonance arthrogaphy of the hip.

| S-EPMC3716221 | biostudies-literature

Diagnosing surface <i>versus</i> bulk reactivity for molecular catalysis within metal-organic frameworks using a quantitative kinetic model.

Project description:Metal-organic frameworks (MOFs) are becoming increasingly popular as heterogenous support matrices for molecular catalysts. Given that reactants, or potentially holes/electrons, need to diffuse into the porous framework as the reaction proceeds, the reaction can possibly take place within the bulk of the particle or be confined to a thin layer at the surface due to transport limitations. Herein, a simple steady-state reaction-diffusion kinetic model is developed to diagnose these two mutually exclusive behaviors in MOF-based systems. The oxygen evolution reaction (OER) driven by a chemical oxidant is presented as an example mechanism. Quantitative metrics for assigning either bulk or surface reactivity are delineated over a wide variety of conditions, and numerical simulations are employed to verify these results. For each case, expressions for the turnover frequency (TOF) are outlined, and it is shown that surface reactivity can influence measured TOFs. Importantly, this report shows how to transition from surface to bulk reactivity and thus identifies which experimental parameters to target for optimizing the efficiency of MOF-based molecular catalyst systems.

| S-EPMC7116375 | biostudies-literature

High-yield intra- and extracellular protein production using Bacillus megaterium.

Project description:The Bacillus megaterium protein production system based on the inducible promoter of the xyl operon (P(xylA)) was systematically optimized. Multiple changes in basic promoter elements, such as the -10 and -35 region and the ribosome-binding site, resulted in an 18-fold increase of protein production compared to the production of the previously established system. The production in shaking-flask culture of green fluorescent protein (Gfp) as a model product led to 82.5 mg per g cell dry weight (g(CDW)) or 124 mg liter(-1). In fed-batch cultivation, the volumetric protein yield was increased 10-fold to 1.25 g liter(-1), corresponding to 36.8 mg protein per g(CDW). Furthermore, novel signal peptides for Sec-dependent protein secretion were predicted in silico using the B. megaterium genome. Subsequently, leader peptides of Vpr, NprM, YngK, YocH, and a computationally designed artificial peptide were analyzed experimentally for their potential to facilitate the secretion of the heterologous model protein Thermobifida fusca hydrolase (Tfh). The best extracellular protein production, 5,000 to 6,200 U liter(-1) (5.3 to 6.6 mg liter(-1)), was observed for strains where the Tfh export was facilitated by a codon-optimized leader peptide of YngK and by the signal peptide of YocH. Further increases in extracellular protein production were achieved when leader peptides were used in combination with the optimized expression system. In this case, the greatest extracellular enzyme amount of 7,200 U liter(-1), 7.7 mg liter(-1), was achieved by YocH leader peptide-mediated protein export. Nevertheless, the observed principal limitations in protein export might be related to components of the Sec-dependent protein transport system.

| S-EPMC2893505 | 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