Stealth Immune Properties of Graphene Oxide Enabled by Surface-Bound Complement Factor H

Belling, Jason N.; Jackman, Joshua A.; Avsar, Saziye Yorulmaz; Park, Jae Hyeon; Wang, Yan; Potroz, Michael G.; Ferhan, Abdul Rahim; Weiss, Paul S.; Cho, Nam‐Joon

doi:10.1021/acsnano.6b05409

Cited by 57 publications

(43 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Li et al similarly observed increased biocompatibility for GO coated with BSA and polyethylene glycol (PEG) . Furthermore, Belling et al demonstrated that albumin adsorption onto the GO surface, partially prevented complement activation . It is reasonable to believe that similar effects are observed with our formulation, which helps to explain the lower cytotoxic effects observed in relation to previously reported data.…”

Section: Discussionsupporting

confidence: 84%

Exfoliation in Endotoxin‐Free Albumin Generates Pristine Graphene with Reduced Inflammatory Properties

et al. 2018

View full text Add to dashboard Cite

mechanical strength. Within the GBMs, pristine graphene (pG) presents key advantages; its virtually defect-free surface enhances its mechanical properties and the absence of oxygen groups increases its electrical and optical conductivity compared to functionalized graphene, [7] presenting opportunities to develop new biomedical devices. Moreover, since no additional chemical modifications are required, the use of pG would have a positive environmental and economic impact over functionalized graphenes, such as graphene oxide (GO). Nevertheless, pG has been less studied in a biological context, due to its intrinsic hydrophobicity, restricting dispersibility and stability in aqueous solution, unless potentially toxic stabilizers are added. Thus, the use of biocompatible dispersants is crucial.We currently lack a complete understanding of the toxic and inflammatory effects of GBMs and conflicting results have been reported. While the toxicity of other graphene-based materials (e.g., GO, rGO), has been extensively studied, [1,[8][9][10] limited work has been done on pristine graphene. [11][12][13] Studies highlight key roles for factors such as lateral size (small vs large), [10] surface functionalization (e.g., GO vs pG), [12,14] purity [15] and hydrophobicity [16] on GBM-cell interaction, thus it is vital to address the intrinsic toxicological effects of pG and elucidate its immunomodulatory properties in order to assess its specific potential as a material for biomedical applications. According Graphene-based materials are under consideration as a new generation of biomaterials for medical applications, owning to their distinctive physicochemical properties. A major obstacle to clinical translation of novel biomaterials is the presence of residual endotoxin contaminants that can trigger deleterious inflammatory responses and unrelated immunomodulatory effects. To overcome this challenge, a liquid exfoliation methodology to prepare endotoxin-free bovine serum albumin (BSA)-exfoliated pristine graphene (EF-Gr) was developed and compared with conventional BSA-exfoliated graphene (C-Gr) and sodium cholate-exfoliated graphene (SC-Gr). In contrast to SC-Gr, protein-exfoliated graphene exhibits low toxicity. Moreover, BSAexfoliated EF-Gr does not trigger cytokine secretion or increase costimulatory molecule expression in dendritic cells (DCs) or macrophages; however it retains the ability to activate the NLRP3 inflammasome in DCs primed withToll-like receptor (TLR) agonists. The results suggest that some reported immunostimulatory effects of graphene preparations may have resulted from contaminants in the formulations. When injected into mice, the inflammatory response induced is comparable in magnitude to that induced by the safe and effective vaccine adjuvant alum. Overall, the study demonstrates the feasibility of producing endotoxin-free pristine graphene that facilitates assessment of the potential of pristine graphene for novel biomedical applications without the confounding effects of toxic and inflammatory conta...

show abstract

Section: Discussionsupporting

confidence: 84%

Exfoliation in Endotoxin‐Free Albumin Generates Pristine Graphene with Reduced Inflammatory Properties

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Complement proteins opsonize pathogens and cells for engulfment via complement receptors and could conceivably promote nanomaterial uptake as well. However, certain complement factors may instead confer “stealth” properties to nanomaterials by preventing further complement activation, as shown in a recent study on GO (43). Complement activation also liberates two potent effector molecules (C3a and C5a) that play important roles in the recruitment and activation of inflammatory cells as well as anaphylaxis, a serious allergic reaction that is rapid in onset and may cause death (44).…”

Section: Bio-corona Formation: Shelter From the Stormmentioning

confidence: 99%

Graphene and the Immune System: A Romance of Many Dimensions

2017

View full text Add to dashboard Cite

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.

show abstract

“…In another approach, Thaxton et al synthesized a suite of high-density lipoprotein-liked NPs which functions to scavenge and neutralize LPS, inhibiting TLR-4 dependent inflammatory response [70]. Moreover, Cho et al demonstrated that NPs coated with negative regulatory complement factor H can prevent complement activation with >90% efficiency [71]. And galactose polymer modified NPs could absorbed complement H protein on their surface in vitro , providing a low level of complement activation [72].…”

Section: Physicochemical Properties Of Nanoparticles Modulate Innamentioning

confidence: 99%

Effects of engineered nanoparticles on the innate immune system

Liu

Hardie

Zhang

et al. 2017

Seminars in Immunology

229

131

View full text Add to dashboard Cite

Engineered nanoparticles (NPs) have broad applications in industry and nanomedicine. When NPs enter the body, interactions with the immune system are unavoidable. The innate immune system, a non-specific first line of defense against potential threats to the host, immediately interacts with introduced NPs and generates complicated immune responses. Depending on their physicochemical properties, NPs can interact with cells and proteins to stimulate or suppress the innate immune response, and similarly activate or avoid the complement system. NPs size, shape, hydrophobicity and surface modification are the main factors that influence the interactions between NPs and the innate immune system. In this review, we will focus on recent reports about the relationship between the physicochemical properties of NPs and their innate immune response, and their applications in immunotherapy.

show abstract

Stealth Immune Properties of Graphene Oxide Enabled by Surface-Bound Complement Factor H

Cited by 57 publications

References 96 publications

Exfoliation in Endotoxin‐Free Albumin Generates Pristine Graphene with Reduced Inflammatory Properties

Exfoliation in Endotoxin‐Free Albumin Generates Pristine Graphene with Reduced Inflammatory Properties

Graphene and the Immune System: A Romance of Many Dimensions

Effects of engineered nanoparticles on the innate immune system

Contact Info

Product

Resources

About