Nanoparticle protein corona evolution: from biological impact to biomarker discovery

Nanoscale ◽  
2022 ◽  
Author(s):  
Nazila Kamaly ◽  
Omid Cameron Farokhzad ◽  
Claudia Corbo
Keyword(s):  
Biomarker Discovery ◽  
Biological Fluids ◽  
Protein Corona ◽  
Biological Impact

Nanoparticles exposed to biological fluids such as blood, quickly interact with their surrounding milieu resulting in a biological coating that results in large part as a function of the physicochemical...

scholarly journals Metabolic Evaluation of Urine from Patients Diagnosed with High Grade (HG) Bladder Cancer by SPME-LC-MS Method

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2194
Author(s):  
Kamil Łuczykowski ◽  
Natalia Warmuzińska ◽  
Sylwia Operacz ◽  
Iga Stryjak ◽  
Joanna Bogusiewicz ◽  
...  
Keyword(s):  
Thin Film ◽  
Bladder Cancer ◽  
High Performance ◽  
Biomarker Discovery ◽  
Solid Phase ◽  
Biological Fluids ◽  
Reversed Phase ◽  
Control Group ◽  
Metabolic Evaluation ◽  
Metabolomic Profiling

Bladder cancer (BC) is a common malignancy of the urinary system and a leading cause of death worldwide. In this work, untargeted metabolomic profiling of biological fluids is presented as a non-invasive tool for bladder cancer biomarker discovery as a first step towards developing superior methods for detection, treatment, and prevention well as to further our current understanding of this disease. In this study, urine samples from 24 healthy volunteers and 24 BC patients were subjected to metabolomic profiling using high throughput solid-phase microextraction (SPME) in thin-film format and reversed-phase high-performance liquid chromatography coupled with a Q Exactive Focus Orbitrap mass spectrometer. The chemometric analysis enabled the selection of metabolites contributing to the observed separation of BC patients from the control group. Relevant differences were demonstrated for phenylalanine metabolism compounds, i.e., benzoic acid, hippuric acid, and 4-hydroxycinnamic acid. Furthermore, compounds involved in the metabolism of histidine, beta-alanine, and glycerophospholipids were also identified. Thin-film SPME can be efficiently used as an alternative approach to other traditional urine sample preparation methods, demonstrating the SPME technique as a simple and efficient tool for urinary metabolomics research. Moreover, this study’s results may support a better understanding of bladder cancer development and progression mechanisms.

scholarly journals Synovial Fluid Profile Dictates Nanopracticle Uptake into Cartilage- Implications of the Protein Corona for Novel Arthitis Treatments

2021 ◽  
Author(s):  
Ula von Mentzer ◽  
Tilia Selldén ◽  
LOISE Råberg ◽  
Gizem Erensoy ◽  
Anna-Karin Hultgård-Ekwall ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Delivery ◽  
Synovial Fluid ◽  
Electrostatic Interactions ◽  
Fetal Calf Serum ◽  
Biological Fluids ◽  
Calf Serum ◽  
Protein Corona ◽  
Drug Delivery Vehicles ◽  
Drug Concentrations

<div>Intra-articular drug delivery strategies aiming to deliver drugs in diseases affected by cartilage-related issues are using electrostatic interactions to penetrate the dense cartilage matrix. This enables delivery of sufficient drug concentrations to the chondrocytes to mediate the desired therapeutic effect. As it is well known that size and charge of nanoparticles affects its interactions with the surrounding biological fluids, where proteins adsorb to the NP surface, resulting in a protein corona. There are, however, no studies investigating how the formed protein coronas affect cartilage uptake and subsequent cellular uptake, nor how they affect other cells present in the synovium of such diseases. Here, we explore the differences between the protein coronas that form when NP are incubated in synovial fluid from osteoarthritic and rheumatoid arthritis patients and compare this to results obtained using fetal calf serum (FCS), as guide for researchers working on joint drug delivery. We demonstrate that the protein corona indeed affects the uptake into cartilage, where there are major differences between the model proteins in fetal calf serum, as compared to synovial fluid from rheumatoid arthritis patients as well as osteoarthritis patients. The data suggests that when developing drug delivery vehicles for joint diseases that leverages electrostatic interactions and size, the interactions with proteins in the biological milieu is highly relevant to consider.</div>

scholarly journals Methodological Approaches to Study Extracellular Vesicle miRNAs in Epstein–Barr Virus-Associated Cancers

2018 ◽  
Vol 19 (9) ◽  
pp. 2810 ◽  
Author(s):  
Li Sun ◽  
David Meckes
Keyword(s):  
Epstein Barr Virus ◽  
Biomarker Discovery ◽  
Immune Escape ◽  
Human Cancer ◽  
Biological Fluids ◽  
Extracellular Vesicle ◽  
Cellular Mirnas ◽  
Barr Virus ◽  
Diagnosis And Prognosis ◽  
Epstein Barr

Epstein Barr-virus (EBV) was the first virus identified to be associated with human cancer in 1964 and is found ubiquitously throughout the world’s population. It is now established that EBV contributes to the development and progression of multiple human cancers of both lymphoid and epithelial cell origins. EBV encoded miRNAs play an important role in tumor proliferation, angiogenesis, immune escape, tissue invasion, and metastasis. Recently, EBV miRNAs have been found to be released from infected cancer cells in extracellular vesicles (EVs) and regulate gene expression in neighboring uninfected cells present in the tumor microenvironment and possibly at distal sites. As EVs are abundant in many biological fluids, the viral and cellular miRNAs present within EBV-modified EVs may serve as noninvasion markers for cancer diagnosis and prognosis. In this review, we discuss recent advances in EV isolation and miRNA detection, and provide a complete workflow for EV purification from plasma and deep-sequencing for biomarker discovery.

scholarly journals Plasma proteins facilitates placental transfer of polystyrene particles

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Michael M. Gruber ◽  
Birgit Hirschmugl ◽  
Natascha Berger ◽  
Magdalena Holter ◽  
Snježana Radulović ◽  
...  
Keyword(s):  
Human Plasma ◽  
Human Placenta ◽  
Plasma Proteins ◽  
Placental Transfer ◽  
Ex Vivo ◽  
Biological Fluids ◽  
Protein Corona ◽  
Human Albumin ◽  
Placental Perfusion ◽  
The Impact

Abstract Background Nanoparticles, which are exposed to biological fluids are rapidly interacting with proteins and other biomolecules forming a corona. In addition to dimension, charge and material the distinct protein corona influences the interplay of nanoparticles with tissue barriers. In this study we were focused on the impact of in situ formed human plasma protein corona on the transfer of 80 nm polystyrene nanoparticles (PS-particles) across the human placenta. To study materno-to fetal PS transfer we used the human ex vivo placental perfusion approach, which represents an intact and physiological tissue barrier. To analyze the protein corona of PS particles we performed shotgun proteomics of isolated nanoparticles before and after tissue exposure. Results Human plasma incubated with PS-particles of 80 nm and subsequent formed protein corona enhanced the transfer across the human placenta compared to PS-corona formed by bovine serum albumin and dextran which served as a control. Quantitative and qualitative changes of plasma proteins determined the changes in PS transfer across the barrier. Based on the analysis of the PS-proteome two candidate proteins, namely human albumin and immunoglobulin G were tested if these proteins may account for the enhanced PS-transfer across the placenta. Interestingly, the protein corona formed by human albumin significantly induced the transfer of PS-particles across the tissue compared to the formed IgG-corona. Conclusion In total we demonstrate the PS corona dynamically and significantly evolves upon crossing the human placenta. Thus, the initial composition of PS particles in the maternal circulation is not predictive for their transfer characteristics and performance once beyond the barrier of the placenta. The precise mechanism of these effects remains to be elucidated but highlights the importance of using well designed biological models when testing nanoparticles for biomedical applications.

A model beyond protein corona: thermodynamics and binding stoichiometries of the interactions between ultrasmall gold nanoclusters and proteins

Nanoscale ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 4573-4585 ◽  
Author(s):  
Miao-Miao Yin ◽  
Wen-Qi Chen ◽  
Ya-Qi Lu ◽  
Jing-Yu Han ◽  
Yi Liu ◽  
...  
Keyword(s):  
Biological Fluids ◽  
Gold Nanoclusters ◽  
Protein Corona

Nanoparticles (NPs) will inevitably interact with proteins and form protein coronas once they are exposed to biological fluids.

scholarly journals Challenges for Biomarker Discovery in Body Fluids Using SELDI-TOF-MS

2010 ◽  
Vol 2010 ◽  
pp. 1-15 ◽  
Author(s):  
Muriel De Bock ◽  
Dominique de Seny ◽  
Marie-Alice Meuwis ◽  
Jean-Paul Chapelle ◽  
Edouard Louis ◽  
...  
Keyword(s):  
Biomarker Discovery ◽  
Biological Fluids ◽  
Protein Profiling ◽  
Sample Collection ◽  
Sample Handling ◽  
Biomarker Identification ◽  
The Past ◽  
Set Up ◽  
And Storage ◽  
Tof Ms

Protein profiling using SELDI-TOF-MS has gained over the past few years an increasing interest in the field of biomarker discovery. The technology presents great potential if some parameters, such as sample handling, SELDI settings, and data analysis, are strictly controlled. Practical considerations to set up a robust and sensitive strategy for biomarker discovery are presented. This paper also reviews biological fluids generally available including a description of their peculiar properties and the preanalytical challenges inherent to sample collection and storage. Finally, some new insights for biomarker identification and validation challenges are provided.

The ProteinChip® Biomarker System from Ciphergen Biosystems: a novel proteomics platform for rapid biomarker discovery and validation

2002 ◽  
Vol 30 (2) ◽  
pp. 82-87 ◽  
Author(s):  
K. Chapman
Keyword(s):  
Biomarker Discovery ◽  
Direct Detection ◽  
Biological Fluids ◽  
Laser Desorption Ionization ◽  
Protein Diversity ◽  
Wide Range ◽  
Surface Enhanced ◽  
Molecular Masses ◽  
Plant Sciences ◽  
Target Binding

Protein biochips are emerging in two distinct formats. The first involves high-density immobilized arrays of recognition molecules (e.g. antibodies), where target binding is monitored indirectly (e.g. via fluorescence). This technology is in its infancy, being limited by the availability of suitable binding molecules that can cope effectively with protein diversity. The second format involves the capture of proteins by biochemical or intermolecular interaction, coupled with direct detection by MS. This technology is available as the ProteinChip® Biomarker System. ProteinChip technology uses surface-enhanced laser desorption/ionization processes to analyse proteins directly from biological samples. Chromatographic surfaces are placed on to ProteinChip Arrays and used to capture subclasses of proteins, dependent on their physical properties. Time-of-flight MS then assigns native molecular masses to the captured proteins. Reproducible protein profiles can be generated from crude biological fluids (e.g. cell lysates, urine or serum). The technology is being applied to a wide range of disciplines, from plant sciences to cancer research, and will be reviewed here.

scholarly journals Interaction of Solid Lipid Nanoparticles and Specific Proteins of the Corona Studied by Surface Plasmon Resonance

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Mauricio E. Di Ianni ◽  
Germán A. Islan ◽  
Cecilia Y. Chain ◽  
Guillermo R. Castro ◽  
Alan Talevi ◽  
...  
Keyword(s):  
Surface Plasmon Resonance ◽  
Polyvinyl Alcohol ◽  
Surface Plasmon ◽  
Plasmon Resonance ◽  
Solid Lipid Nanoparticles ◽  
Chemical Nature ◽  
Biological Fluids ◽  
Protein Corona ◽  
Lipid Nanoparticles ◽  
Solid Lipid

The applications of pharmaceutical and medical nanosystems are among the most intensively investigated fields in nanotechnology. A relevant point to be considered in the design and development of nanovehicles intended for medical use is the formation of the “protein corona” around the nanoparticle, that is, a complex biomolecular layer formed when the nanovehicle is exposed to biological fluids. The chemical nature of the protein corona determines the biological identity of the nanoparticle and influences, among others, the recognition of the nanocarrier by the mononuclear phagocytic system and, thus, its clearance from the blood. Recent works suggest that Surface Plasmon Resonance (SPR), extensively employed for the analysis of biomolecular interactions, can shed light on the formation of the protein corona and its interaction with the surroundings. The synthesis and characterization of solid lipid nanoparticles (SLN) coated with polymers of different chemical nature (e.g., polyvinyl alcohol, chitosans) are reported. The proof-of-concept for the use of SPR technique in characterizing protein-nanoparticle interactions of surface-immobilized proteins (immunoglobulin G and bovine serum albumin, both involved in the formation of the corona) subjected to flowing SLN is demonstrated for non-chitosan-coated nanoparticles. All assayed nanosystems show more preference for IgG than for BSA, such preference being more pronounced in the case of polyvinyl-alcohol-coated SLN.

scholarly journals Proteomic analysis of extracellular vesicles in cerebrospinal fluid of patients with Alzheimer’s disease

2020 ◽  
Author(s):  
Davide Chiasserini ◽  
Irene Bijnsdorp ◽  
Giovanni Bellomo ◽  
Pier Luigi Orvietani ◽  
Sander R. Piersma ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Extracellular Vesicles ◽  
Biomarker Discovery ◽  
Neurodegenerative Disorder ◽  
High Resolution Mass Spectrometry ◽  
Biological Fluids ◽  
Protein Profile ◽  
Protein Markers

AbstractCerebrospinal fluid (CSF) contains different types of extracellular vesicles (EVs) with undisclosed biomarker potential for neurodegenerative diseases. The aims of the present study were: i) to compare the proteome EVs isolated using different ultracentrifugation speed ii) to preliminary explore the EVs proteome in a common neurodegenerative disorder, Alzheimer’s disease (AD) compared to neurological controls. CSF samples from control subjects and AD patients were pooled separately (15 mL) and subjected to ultracentrifugation (UC) at different speeds (20,000g and 100,000g) to isolate separate EV fractions (P20 and P100). The proteome was analysed using high-resolution mass spectrometry (LC-MS/MS) and comparisons were made using bioinformatic analysis. EVs isolated at 100,000g (P100) had a proteome consistent with vesicles secreted via an ESCRT-dependent mechanism, being highly enriched in alix (PDCD6IP), syntenin-1 (SDCBP) and TSG101. EVs isolated at 20,000g were substantially different, showing enrichment in cytoskeletal and cell adhesion molecules. The pools from patients diagnosed with AD showed a distinct protein profile of CSF EVs, with increased levels of ADAM10, SPON1, CH3IL1 and MDK in the P100 fraction. CSF EV offer a new potential biosource of protein markers for AD detection and a complementary framework to the analysis of whole biological fluids for biomarker discovery.

scholarly journals Particle-by-Particle in Situ Characterization of the Protein Corona via Real-Time 3D Single Particle Tracking Microscopy

2021 ◽  
Author(s):  
Xiaochen Tan ◽  
Kevin Welsher
Keyword(s):  
Real Time ◽  
Particle Tracking ◽  
Single Particle ◽  
Biological Fluids ◽  
Protein Corona ◽  
Single Particle Tracking ◽  
Ex Situ ◽  
High Background ◽  
Particle Nature

<p>Nanoparticles (NPs) adsorb proteins when exposed to biological fluids, forming a dynamic protein corona that affects their fate in biological environments. A comprehensive understanding of the protein corona is lacking due to the inability of current techniques to precisely measure the full corona <i>in situ</i> at the single particle level. Herein, we introduce a 3D real-time single-particle tracking spectroscopy to "lock-on" to single freely-diffusing polystyrene NPs and probe their individual protein coronas. The diffusive motions of the tracked NPs enable quantification of the "hard corona" using mean-squared displacement analysis. Critically, this method's particle-by-particle nature enabled a lock-in-type frequency filtering approach to extract the full protein corona, despite the typically confounding effect of high background signal from unbound proteins. From these results, the dynamic <i>in situ </i>full protein corona is observed to contain double the number of proteins than are observed in the <i>ex situ</i> measured "hard" protein corona.</p><br>

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