Graphene and the Immune System: A Romance of Many Dimensions

Graphene-based materials (GBMs) are emerging as attractive materials for biomedical applications. Understanding how these materials are perceived by and interact with the immune system is of fundamental importance. Phagocytosis is a major mechanism deployed by the immune system to remove pathogens, particles, and cellular debris. Here, we discuss recent studies on the interactions of GBMs with different phagocytic cells, including macrophages, neutrophils, and dendritic cells. The importance of assessing GBMs for endotoxin contamination is discussed as this may skew results. We also explore the role of the bio-corona for interactions of GBMs with immune cells. Finally, we highlight recent evidence for direct plasma membrane interactions of GBMs.

• Publication year

  2017

• Venue

  Frontiers in Immunology

• Publication date

  2017-06-13

• Fields of study

  Biology, Medicine, Materials Science

• Identifiers
  DOI 10.3389/fimmu.2017.00673PMID 28659915PMCID 5468375
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Faculty Opinions recommendation of Inflammasomes: mechanism of assembly, regulation and signalling.

  2018cited by this paper
• Graphene-Induced Pore Formation on Cell Membranes

  2017cited by this paper
• An emerging role for neutrophil extracellular traps in noninfectious disease

  2017cited by this paper
• Graphene and carbon nanotubes activate different cell surface receptors on macrophages before and after deactivation of endotoxins

  2017cited by this paper
• Graphene Oxide Induced Perturbation to Plasma Membrane and Cytoskeletal Meshwork Sensitize Cancer Cells to Chemotherapeutic Agents.

  2017cited by this paper
• Carbon Nanotubes Activate Limulus Amebocyte Lysate Coagulation by Interface Adsorption.

  2017cited by this paper
• Phenotype Determines Nanoparticle Uptake by Human Macrophages from Liver and Blood.

  2017cited by this paper
• Culture Media Critically Influence Graphene Oxide Effects on Plasma Membranes

  2017cited by this paper
• Hollow carbon spheres trigger inflammasome-dependent IL-1β secretion in macrophages

  2017cited by this paper
• Biodegradation of Carbon Nanotubes, Graphene, and Their Derivatives.

  2017cited by this paper
• Biomolecular Coronas Provide the Biological Identity of Nanomaterials

  2017cited by this paper
• Macrophage activation status determines the internalization of mesoporous silica particles of different sizes: Exploring the role of different pattern recognition receptors.

  2017cited by this paper
• Inflammasomes: mechanism of assembly, regulation and signalling

  2016cited by this paper
• Molecular and Genomic Impact of Large and Small Lateral Dimension Graphene Oxide Sheets on Human Immune Cells from Healthy Donors

  2016cited by this paper
• The Intracellular Destiny of the Protein Corona: A Study on its Cellular Internalization and Evolution.

  2016cited by this paper
• Spontaneous Protein Adsorption on Graphene Oxide Nanosheets Allowing Efficient Intracellular Vaccine Protein Delivery.

  2016cited by this paper
• Biological interactions of carbon-based nanomaterials: From coronation to degradation.

  2016cited by this paper
• Protein adsorption is required for stealth effect of poly(ethylene glycol)- and poly(phosphoester)-coated nanocarriers.

  2016cited by this paper
• Controlling the Stealth Effect of Nanocarriers through Understanding the Protein Corona.

  2016cited by this paper
• Nanoparticles size-dependently initiate self-limiting NETosis-driven inflammation

  2016cited by this paper
• Regulation of Macrophage Recognition through the Interplay of Nanoparticle Surface Functionality and Protein Corona.

  2016cited by this paper
• Graphene Oxides Decorated with Carnosine as an Adjuvant To Modulate Innate Immune and Improve Adaptive Immunity in Vivo.

  2016cited by this paper
• Improved In Vitro and In Vivo Biocompatibility of Graphene Oxide through Surface Modification: Poly(Acrylic Acid)-Functionalization is Superior to PEGylation.

  2016influential reference
• In vitro and in vivo comparison of the immunotoxicity of single- and multi-layered graphene oxides with or without pluronic F-127

  2016cited by this paper
• Graphene Oxide Nanosheets Stimulate Ruffling and Shedding of Mammalian Cell Plasma Membranes.

  2016cited by this paper
• Soluble and immobilized graphene oxide activates complement system differently dependent on surface oxidation state.

  2016cited by this paper
• Endotoxin contamination: a key element in the interpretation of nanosafety studies.

  2016cited by this paper
• Functionalized graphene oxide serves as a novel vaccine nano-adjuvant for robust stimulation of cellular immunity.

  2016influential reference
• Detection of Endotoxin Contamination of Graphene Based Materials Using the TNF-α Expression Test and Guidelines for Endotoxin-Free Graphene Oxide Production

  2016cited by this paper
• Stealth Immune Properties of Graphene Oxide Enabled by Surface-Bound Complement Factor H.

  2016cited by this paper
• Vacuolization in Cytoplasm and Cell Membrane Permeability Enhancement Triggered by Micrometer-Sized Graphene Oxide.

  2015cited by this paper
• Postulates for validating TLR4 agonists

  2015cited by this paper
• Surface-engineered graphene navigate divergent biological outcomes toward macrophages.

  2015cited by this paper
• It takes two to tango: Understanding the interactions between engineered nanomaterials and the immune system.

  2015cited by this paper
• Neutrophil extracellular traps license macrophages for cytokine production in atherosclerosis

  2015cited by this paper
• Crucial Role of Lateral Size for Graphene Oxide in Activating Macrophages and Stimulating Pro-inflammatory Responses in Cells and Animals.

  2015cited by this paper
• Graphene Induces Formation of Pores That Kill Spherical and Rod-Shaped Bacteria.

  2015cited by this paper
• Protein corona mitigates the cytotoxicity of graphene oxide by reducing its physical interaction with cell membrane.

  2015cited by this paper
• NADPH Oxidase-Dependent NLRP3 Inflammasome Activation and its Important Role in Lung Fibrosis by Multiwalled Carbon Nanotubes.

  2015cited by this paper
• Science and technology roadmap for graphene, related two-dimensional crystals, and hybrid systems.

  2015influential reference
• Potential toxicity of graphene to cell functions via disrupting protein-protein interactions.

  2015cited by this paper
• Use of a pro-fibrogenic mechanism-based predictive toxicological approach for tiered testing and decision analysis of carbonaceous nanomaterials.

  2015cited by this paper
• Reduced Cytotoxicity of Graphene Nanosheets Mediated by Blood-Protein Coating.

  2015cited by this paper
• Extracellular HMGB1 regulates multi-walled carbon nanotube-induced inflammation in vivo

  2015cited by this paper
• Classification framework for graphene-based materials.

  2014cited by this paper
• Protein corona fingerprinting predicts the cellular interaction of gold and silver nanoparticles.

  2014influential reference
• Neutrophils sense microbial size and selectively release neutrophil extracellular traps in response to large pathogens

  2014influential reference
• Assembly and localization of Toll-like receptor signalling complexes

  2014cited by this paper
• Exploring the Interface of Graphene and Biology

  2014cited by this paper
• Graphene Oxide Attenuates Th2-Type Immune Responses, but Augments Airway Remodeling and Hyperresponsiveness in a Murine Model of Asthma

  2014cited by this paper
• Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines

  2014influential reference
• Interference of silica nanoparticles with the traditional Limulus amebocyte lysate gel clot assay

  2014cited by this paper
• Prospects and Challenges of Graphene in Biomedical Applications

  2013cited by this paper
• Graphene oxide induces toll-like receptor 4 (TLR4)-dependent necrosis in macrophages.

  2013cited by this paper
• Functionalization of carbon nanoparticles modulates inflammatory cell recruitment and NLRP3 inflammasome activation.

  2013cited by this paper
• Evidencing the mask effect of graphene oxide: a comparative study on primary human and murine phagocytic cells.

  2013cited by this paper
• Graphene oxide, but not fullerenes, targets immunoproteasomes and suppresses antigen presentation by dendritic cells.

  2013cited by this paper
• Single-walled carbon nanotube surface control of complement recognition and activation.

  2013influential reference
• Surface polyethylene glycol conformation influences the protein corona of polyethylene glycol-modified single-walled carbon nanotubes: potential implications on biological performance.

  2013cited by this paper
• Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology.

  2013cited by this paper
• Graphene microsheets enter cells through spontaneous membrane penetration at edge asperities and corner sites

  2013cited by this paper
• Engineering an effective immune adjuvant by designed control of shape and crystallinity of aluminum oxyhydroxide nanoparticles.

  2013cited by this paper
• Enzyme-catalyzed Degradation of Carbon Nanomaterials

  2013cited by this paper
• Mechanisms of carbon nanotube-induced toxicity: focus on pulmonary inflammation.

  2013cited by this paper
• Destructive extraction of phospholipids from Escherichia coli membranes by graphene nanosheets.

  2013cited by this paper
• Functionalization of graphene oxide generates a unique interface for selective serum protein interactions.

  2013cited by this paper
• Decisions about dendritic cells: past, present, and future.

  2012cited by this paper
• Biomolecular coronas provide the biological identity of nanosized materials.

  2012cited by this paper
• Factors controlling nanoparticle pharmacokinetics: an integrated analysis and perspective.

  2012cited by this paper
• Biological interactions of graphene-family nanomaterials: an interdisciplinary review.

  2012cited by this paper
• A natural vanishing act: the enzyme-catalyzed degradation of carbon nanomaterials.

  2012cited by this paper
• Designing the nanoparticle-biomolecule interface for "targeting and therapeutic delivery".

  2012cited by this paper
• Contamination of nanoparticles by endotoxin: evaluation of different test methods

  2012cited by this paper
• Simultaneous induction of autophagy and toll-like receptor signaling pathways by graphene oxide.

  2012cited by this paper
• Alum interaction with dendritic cell membrane lipids is essential for its adjuvanticity

  2011cited by this paper
• Differential uptake of functionalized polystyrene nanoparticles by human macrophages and a monocytic cell line.

  2011cited by this paper
• Long, needle-like carbon nanotubes and asbestos activate the NLRP3 inflammasome through a similar mechanism.

  2011cited by this paper
• Binding of blood proteins to carbon nanotubes reduces cytotoxicity

  2011cited by this paper
• Macrophages and tissue injury: agents of defense or destruction?

  2011influential reference
• Graphene oxide sheets at interfaces.

  2010cited by this paper
• Complement activation cascade triggered by PEG-PL engineered nanomedicines and carbon nanotubes: the challenges ahead.

  2010cited by this paper
• Lipid Rafts As a Membrane-Organizing Principle

  2010cited by this paper
• Carbon nanotube-based nanocarriers: the importance of keeping it clean.

  2010cited by this paper
• Ambiguities in applying traditional Limulus amebocyte lysate tests to quantify endotoxin in nanoparticle formulations.

  2010cited by this paper
• The chemistry of graphene oxide.

  2010cited by this paper
• NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals

  2010cited by this paper
• Complement: a key system for immune surveillance and homeostasis

  2010cited by this paper
• NLRP3 inflamasomes are required for atherogenesis and activated by cholesterol crystals that form early in disease

  2010cited by this paper
• Particle size and activation threshold: a new dimension of danger signaling.

  2010cited by this paper
• Evaluation of nanoparticle immunotoxicity.

  2009cited by this paper
• NETs: a new strategy for using old weapons.

  2009cited by this paper
• Wettability and surface free energy of graphene films.

  2009cited by this paper
• Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants

  2008cited by this paper
• Alum adjuvanticity: Unraveling a century old mystery

  2008cited by this paper
• Cutting Edge: Alum Adjuvant Stimulates Inflammatory Dendritic Cells through Activation of the NALP3 Inflammasome

  2008cited by this paper
• Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts

  2008cited by this paper
• Understanding the nanoparticle–protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles

  2007cited by this paper
• Complement activation and protein adsorption by carbon nanotubes.

  2006influential reference
• The importance of an endotoxin-free environment during the production of nanoparticles used in medical applications.

  2006cited by this paper
• Neutrophils and immunity: challenges and opportunities

  2006cited by this paper

• The Influence of Carbon Nanotubes and Graphene on Immune Cells

  2025cites this paper
• 3D printing of nanoparticle-containing scaffolds for cancer phototherapy, magnetic hyperthermia therapy, and tissue regeneration.

  2025cites this paper
• Graphene-based materials are not skin sensitizers: adoption of the in chemico/in vitro OECD test guidelines.

  2025cites this paper
• Nanotechnology in Neuro-Oncology: Evaluating the Potential of Graphene and Boron Nitride Nanostructures

  2025cites this paper
• Modification of low nickel biograde stainless steel with graphene oxide for enhanced corrosion resistance and in vivo biocompatibility

  2025cites this paper
• Formation of bone tissue apatite on starch-based nanofiber-capped nanohydroxyapatite and reduced graphene oxide: a preliminary study

  2024cites this paper
• Biocompatibility of Water‐Dispersible Pristine Graphene and Graphene Oxide Using a Close‐to‐Human Animal Model: A Pilot Study on Swine

  2024cites this paper
• Biodegradability of Partially Reduced Nanographene Oxide by Human, Plant and Microbial Enzymes: Impact of Magnetic Nanoparticles

  2024cites this paper
• Mitigative Effect of Graphene Oxide Nanoparticles in Maintaining Gut–Liver Homeostasis against Alcohol Injury

  2024cites this paper
• Design Principles for Immunomodulatory Biomaterials.

  2024cites this paper
• Carbon‐Based Nanomaterials for Antiviral Applications

  2024cites this paper
• A Narrative Review on the Promising Potential of Graphene in Vaccine Design: Evaluating the Benefits and Drawbacks of Carbon Nanoplates in Nanovaccine Production

  2024cites this paper
• Perilous paradigm of graphene oxide and its derivatives in biomedical applications: Insight to immunocompatibility.

  2024cites this paper
• Graphene Oxide (GO)-Based Bioink with Enhanced 3D Printability and Mechanical Properties for Tissue Engineering Applications

  2024cites this paper
• TPG-functionalized PLGA/PCL nanofiber membrane facilitates periodontal tissue regeneration by modulating macrophages polarization via suppressing PI3K/AKT and NF-κB signaling pathways

  2024cites this paper
• Enriched Graphene Oxide-Polypropylene Suture Threads Buttons Modulate the Inflammatory Pathway Induced by Escherichia coli Lipopolysaccharide

  2023cites this paper
• Defect Engineering of Cvd Graphene and Real-Time Raman Study of No2 Adsorption Toward Enhanced Sensing Sensitivity

  2023cites this paper
• Graphene-Based Material-Mediated Immunomodulation in Tissue Engineering and Regeneration: Mechanism and Significance.

  2023cites this paper
• Application of Graphene Oxide in Oral Surgery: A Systematic Review

  2023cites this paper
• Engineering the glioblastoma microenvironment using TLR7/8 agonist-complexed graphene oxide nanosheets

  2023cites this paper
• Graphene- and MXene-based materials for neuroscience: diagnostic and therapeutic applications.

  2023cites this paper
• Targeted Drug Delivery Systems for Curcumin in Breast Cancer Therapy

  2023cites this paper
• Immunotoxicity of Carbon-Based Nanomaterials, Starring Phagocytes

  2022cites this paper
• Understanding the bidirectional interactions between two-dimensional materials, microorganisms, and the immune system.

  2022cites this paper
• Hazard assessment of abraded thermoplastic composites reinforced with reduced graphene oxide.

  2022cites this paper
• Controllable graphene oxide-based biocompatible hybrid interface as an anti-fibrotic coating for metallic implants

  2022cites this paper
• 2D Materials for Cardiac Tissue Repair and Regeneration

  2022cites this paper
• Recent advances and challenges in graphene-based nanocomposite scaffolds for tissue engineering application.

  2022cites this paper
• The Effect of Pristine and Pegylated Graphene Oxide Nanosheets on the Functions of Human Neutrophils

  2022cites this paper
• Nanoparticle-induced immune response: Health risk versus treatment opportunity?

  2022cites this paper
• Silver Nanoparticle‐Decorated Reduced Graphene Oxide Nanomaterials Exert Membrane Stress and Induce Immune Response to Inhibit the Early Phase of HIV‐1 Infection

  2022cites this paper
• Graphene quantum dots disturbed the energy homeostasis by influencing lipid metabolism of macrophages.

  2022cites this paper
• Graphene and its derivatives: "one stone, three birds" strategy for orthopedic implant-associated infections.

  2022cites this paper
• Flake Graphene-Based Nanomaterial Approach for Triggering a Ferroptosis as an Attractive Theranostic Outlook for Tackling Non-Small Lung Cancer: A Mini Review

  2022cites this paper
• Graphene oxide modulates dendritic cell ability to promote T cell activation and cytokine production.

  2022cites this paper
• Graphene oxide activates B cells with upregulation of granzyme B expression: evidence at the single-cell level for its immune-modulatory properties and anticancer activity.

  2021cites this paper
• Gold Nanoparticles and Graphene Oxide Flakes Synergistic Partaking in Cytosolic Bactericidal Augmentation: Role of ROS and NOX2 Activity

  2021cites this paper
• Carbon nanomaterials for cardiovascular theranostics: Promises and challenges

  2021cites this paper
• Carbon-Based Nanomaterials: Promising Antiviral Agents to Combat COVID-19 in the Microbial-Resistant Era

  2021cites this paper
• Altered immune cells in the liver and spleen of mice as a typical immune response to graphene oxide exposure

  2021cites this paper
• Stimulation of Innate and Adaptive Immune Cells with Graphene Oxide and Reduced Graphene Oxide Affect Cancer Progression

  2021cites this paper
• Carbon-Based Nanomaterials Increase Reactivity of Primary Monocytes towards Various Bacteria and Modulate Their Differentiation into Macrophages

  2021cites this paper
• Modulating Osteoimmune Responses by Mesoporous Silica Nanoparticles.

  2021cites this paper
• Stimulation of Innate and Adaptive Immune Cells with Graphene Oxide and Reduced Graphene Oxide Affect Cancer Progression

  2021cites this paper
• Few Layer Graphene Does Not Affect Cellular Homeostasis of Mouse Macrophages

  2020cites this paper
• An Immunological Approach to the Biocompatibility of Mesoporous SiO2-CaO Nanospheres

  2020cites this paper
• Graphene, other carbon nanomaterials and the immune system: toward nanoimmunity-by-design

  2020cites this paper
• Curcumin Complexed with Graphene Derivative for Breast Cancer Therapy.

  2020cites this paper
• Blood exposure to graphene oxide may cause anaphylactic death in non-human primates

  2020cites this paper
• Toward High-Dimensional Single-Cell Analysis of Graphene Oxide Biological Impact: Tracking on Immune Cells by Single-Cell Mass Cytometry.

  2020cites this paper
• Hemocompatibility of Carbon Nanostructures

  2020cites this paper
• Nanomaterials and Neutrophils

  2020cites this paper
• Impact of the surface functionalization on nanodiamond biocompatibility: a comprehensive view on human blood immune cells

  2020cites this paper
• Gadolinium labelled nanoliposomes as the platform for MRI theranostics: in vitro safety study in liver cells and macrophages

  2020cites this paper
• Proinflammatory Effect of Carbon-Based Nanomaterials: In Vitro Study on Stimulation of Inflammasome NLRP3 via Destabilisation of Lysosomes

  2020cites this paper
• Highly Oxidized Graphene Quantum Dots from Coal as Efficient Antioxidants.

  2019cites this paper
• "Ultramixing": A Simple and Effective Method To Obtain Controlled and Stable Dispersions of Graphene Oxide in Cell Culture Media.

  2019cites this paper
• Differential Immunomodulatory Effect of Graphene Oxide and Vanillin-Functionalized Graphene Oxide Nanoparticles in Human Acute Monocytic Leukemia Cell Line (THP-1)

  2019cites this paper
• Skin irritation potential of graphene-based materials using a non-animal test.

  2019cites this paper
• The molecular mechanism of robust macrophage immune responses induced by PEGylated molybdenum disulfide.

  2019cites this paper
• Assessing the Adverse Effects of Two-Dimensional Materials Using Cell Culture-Based Models

  2019cites this paper
• Nano-bio interactions: a neutrophil-centric view

  2019cites this paper
• Graphene oxide touches blood: in vivo interactions of bio-coronated 2D materials.

  2019cites this paper
• Cytokine Profiling of Primary Human Macrophages Exposed to Endotoxin‐Free Graphene Oxide: Size‐Independent NLRP3 Inflammasome Activation

  2018cites this paper
• Occupational exposure to graphene based nanomaterials: risk assessment.

  2018cites this paper
• Macrophage sensing of single-walled carbon nanotubes via Toll-like receptors

  2018cites this paper
• Perspective: 2D for beyond CMOS

  2018cites this paper
• Graphene Oxide Elicits Membrane Lipid Changes and Neutrophil Extracellular Trap Formation

  2018cites this paper
• Brain Theranostics and Radiotheranostics: Exosomes and Graphenes In Vivo as Novel Brain Theranostics

  2018cites this paper
• Safety Assessment of Graphene-Based Materials: Focus on Human Health and the Environment.

  2018cites this paper
• Immunological impact of graphene oxide sheets in the abdominal cavity is governed by surface reactivity

  2018cites this paper
• Graphene oxide nanosheets increase Candida albicans killing by pro-inflammatory and reparative peritoneal macrophages.

  2018cites this paper
• Novel Anti-Tuberculosis Nanodelivery Formulation of Ethambutol with Graphene Oxide

  2017cites this paper
• Nanoparticles and innate immunity: new perspectives on host defence.

  2017cites this paper
• The In(cid:976)luence of Nanoparticles of Graphene Oxide‑PEG on Cytokine Pro(cid:976)ile of Monocytes from Human Blood In Vitro

  year unknowncites this paper