The Biological Identity of Metal-Organic Framework through Profiling Proteomic Fingerprinting of Protein Corona
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus Musculus Bos Taurus
SUBMITTER: 
Jigang Wang
PROVIDER: PXD061202 | iProX | Tue Feb 25 00:00:00 GMT 2025
REPOSITORIES: iProX
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Project description:This scenario was designed to investigate the protein corona pattern on the pillar-layer surface of a Cu-based metal-organic framework (MOF) in human plasma. The [Cu(L)(L/)].1.3DMA (MOF-1) {L = 4, 4/-bipyridine and L/ = 5-aminoisophthalic acid}, was synthesized through the sonochemical irradiation approach as well as characterized by various techniques like scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray powder diffraction and single-crystal X-ray diffraction. The space group was determined to be an orthorhombic space group (Pbam) by single-crystal X-ray diffraction. Single-crystal X-ray analyses on MOF-1 showed that Cu+2 ion was 6-coordinated. Besides, to study and clarify interactions between MOFs and biological milieu, human whole blood plasma was selected as a model. Fluorescence spectroscopy and SDS-PAGE techniques were employed to explore quantitative and qualitative in situ characterization of protein corona as well. Furthermore, cell viability in a cancerous cell lines was evaluated by MTT assay in the presence and absence of the corona. The results from SDS-PAGE illustrated that the most adsorbed quantity among plasma proteins belongs to fibrinogen (α, β and γ chains), and this protein showed the maximum frequency on the MOF-1s surface, so the possible interactions of MOF-1s with fibrinogen also studied using fluorescence spectroscopy and corresponding data were plotted. According to the obtained data from MTT assay, these structures have concentration-dependent toxicity. In brief, based on the obtained data in the current study, the designed MOF can be introduced as a new desirable carrier for drug/gen delivery after further prerequisite assessments.
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Project description:Aging profoundly influences the composition of biological fluids, including the plasma proteome and lipidome, yet its effects on the protein coronas (PC) forming around nanoparticles (NPs) remain poorly understood. Here, we investigate how age-dependent changes in plasma proteins and lipids modulate the PC on silica NPs, affecting their physicochemical properties, cellular interactions, immune responses, and in vivo pharmacokinetics. Using plasma from C57 mice at 1, 9, and 18 months of age, we demonstrate that while lipid composition remains relatively stable, the PCs have subtle distinct age-related shifts. Proteomic analyses reveal altered abundances of proteins involved in endocytosis, cell adhesion, and immune regulation, ultimately influencing macrophage uptake and activation. In vitro experiments show that younger plasma-derived coronas enhance NP internalization, whereas older coronas diminish uptake but promote a stronger inflammatory response via complement activation and NF-κB signaling. In senescent macrophages, the pattern of NP internalization and immune activation differs, highlighting the complexity of age-associated changes in host-NP interactions. In vivo studies further confirm that NPs biodistribution, biocompatibility, and immunogenicity vary significantly with host age. our findings suggest age as a crucial yet underexplored factor in the design of nanomedicine, with significant implications for enhancing the safety and efficacy of both diagnostic and therapeutic nanomedicine technologies.
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Project description:a new hybrid method, which integrates direct infusion shotgun proteome analysis (DISPA) with nanoparticle (NP) protein coronas enrichment for high throughput and efficient plasma proteomic profiling.
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Project description:A high-throughput workflow for bottom-up proteomics (BUP) of human plasma using capillary zone electrophoresis-tandem mass spectrometry (CZE-MS/MS) and nanoparticle protein corona-assisted sample preparation is presented. The streamlined approach enabled the identification and quantification of hundreds of proteins from plasma/serum samples in 3.5 hours from sample to data. Nanoparticles with varied physiochemical properties studied in this work captured different pools of the plasma/serum proteome in the protein coronas, and the protein corona-based sample preparation approach enabled the measurement of low-abundance proteins compared to the approach without nanoparticles. Applying this high-throughput workflow to serum samples of a mouse NUT carcinoma (NC) cancer model allowed the determination of differentially expressed serum proteins between NC bearing mice and healthy controls. By comparing our quantitative proteomics data with published transcriptomics data, we revealed a handful of potential serum protein biomarkers of NC cancer (e.g., secreted phosphoprotein 1, Spp1). We expect this high-throughput workflow, with additional improvement in the speed of the mass spectrometer, will be useful for advancing the discovery of new protein biomarkers of diseases (e.g., cancer) using plasma/serum samples valuable for liquid biopsy applications.
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Project description:The MS data set contains the result from HDL VLDL corona used in the publication, titled Multiomics analysis of naturally efficacious LNP coronas reveals high-density lipoprotein is necessary for LNP function.
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Project description:The MS data set contains the result from each individual rat plasma derived corona used in the publication, titled Multiomics analysis of naturally efficacious LNP coronas reveals high-density lipoprotein is necessary for LNP function.
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Project description:Upon entering in contact with the biological environment, nanostructures are immediately covered by biomolecules, and in particular proteins forming the so-called “protein corona” (PC). The phenomenon of PC formation has gained great attention in recent years due to its implication for the use of nanostructures in biomedicine. In fact, it has been shown that the formation of the PC can impact the performance of nanostructures by reducing their stability, causing aggregation, increasing their toxicity, and causing unexpected and undesired nanostructure-cell interactions. In this work, we decided to study for the first time the formation and the evolution of PC on the surface of nanostructured lipid carriers loaded with superparamagnetic iron oxide nanoparticles (SPIONs), before and after the crossing of an in vitro model of the blood-brain barrier. Combining confocal microscopy, direct STochastic Optical Reconstruction Microscopy (dSTORM), and proteomic analysis, we were able to provide a complete analysis of the PC formation and evolution. In particular, we evidence that PC formation is a fast process, being formed around particles even after just 1 min of exposure to fetal bovine serum. Moreover, PC formed around particles is extremely heterogeneous: while some particles have no associated PC at all, others are completely covered by proteins. Lastly, the interaction with an in vitro blood-brain barrier model strongly affects the PC composition: in particular, a large amount of the proteins forming the initial PC is lost after the BBB passage and is partially replaced by new proteins derived from both the brain endothelial cells and from the cell culture medium. Altogether, the presented data could potentially provide new insights into the design and fabrication of lipid nanostructures for the treatment of central nervous system disorders.
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Project description:Crystalline metal organic framework (MOF) materials containing interconnected porosity can be chemically modified to promote stimulus-driven (light, magnetic or electric fields) structural transformations that can be used in a number of devices. Innovative research strategies are now focused on understanding the role of chemical bond manipulation to reversibly alter the free volume in such structures of critical importance for electro-catalysis, molecular electronics, energy storage technologies, sensor devices and smart membranes. In this letter, we study the mechanism for which an electrically switchable MOF composed of Cu(TCNQ) (TCNQ = 7,7,8,8-tetracyanoquinodimethane) transitions from a high-resistance state to a conducting state in a reversible fashion by an applied potential. The actual mechanism for this reversible electrical switching is still not understood even though a number of reports are available describing the application of electric-field-induced switching of Cu(TCNQ) in device fabrication.
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