Biomimetic and synthetic interfaces to tune immune responses (Review)

Garapaty, Anusha; Champion, Julie A.

doi:10.1116/1.4922798

“…Nano- and micro particles have been developed to tailor immune responses including enhancement of vaccine responses to pathogens, drug delivery to inflamed cells, and modulation of inflammation in antigen-specific or non-specific manners [1]. New strategies are being explored to control immune functions and particle properties play a key role in programming cellular responses.…”

Section: Introductionmentioning

confidence: 99%

Shape of ligand immobilized particles dominates and amplifies the macrophage cytokine response to ligands

Garapaty

¹

,

Champion

²

2019

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Macrophages aid in clearing synthetic particulates introduced into the body and bridge innate and adaptive immunity through orchestrated secretion of cytokines and chemokines. While the field has made tremendous progress in understanding the effect of particle physicochemical properties on particle-macrophage interactions, it is not known how macrophage functions like cytokine production are affected while presenting active ligands on particles with altered physical properties. Moreover, it is unknown if ligand presentation through an altered particle shape can elicit differential macrophage cytokine responses and if responses are ligand dependent. Therefore, we investigated the influence of geometric particle presentation of diverse ligands, bovine serum albumin, immunoglobulin-G and ovalbumin, on macrophage inflammatory cytokine response. Our results indicate that for similar ligand densities, ligand presentation on rods enhanced production of inflammatory cytokine tumor necrosis factor-alpha (TNF-α) compared to spheres regardless of the nature of the ligand and its cellular receptor. Surprisingly, TNF-α responses were affected by ligand density in a shape-dependent manner and did not correlate to total particle-macrophage association. This study demonstrates the ability of geometric manipulation of particle ligands to alter macrophage cytokine response irrespective of the nature of the ligand.

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“…The initiation, maintenance,a nd suppression of immune responses mostly depend upon the communication occurring at the natural interfaces. [1] Thec ell-cell or cell-particulate interface plays an essential role in directing the behavior of immune systems and inspire the design of nanoparticles (NPs) with immune activity. [1c, 2] Thef unction of NPs in tuning the immune response is determined by the physicochemical properties of the NP surfaces.…”

mentioning

confidence: 99%

Mitigation of Inflammatory Immune Responses with Hydrophilic Nanoparticles

Li

¹

,

Xie

²

,

Yuan

³

et al. 2018

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While hydrophobic nanoparticles (NPs) have been long recognized to boost the immune activation, whether hydrophilic NPs modulate an immune system challenged by immune stimulators and how their hydrophilic properties may affect the immune response is still unclear. To answer this question, three polymers, poly(ethylene glycol) (PEG), poly(sulfobetaine) (PSB) and poly(carboxybetaine) (PCB), which are commonly considered hydrophilic, are studied in this work. For comparison, nanogels with uniform size and homogeneous surface functionalities were made from these polymers. Peripheral blood mononuclear cells (PBMCs) stimulated by lipopolysaccharide (LPS) and an LPS-induced lung inflammation murine model were used to investigate the influence of nanogels on the immune system. Results show that the treatment of hydrophilic nanogels attenuated the immune responses elicited by LPS both in vitro and in vivo. Moreover, we found that PCB nanogels, which have the strongest hydration and the lowest non-specific protein binding, manifested the best performance in alleviating the immune activation, followed by PSB and PEG nanogels. This reveals that the immunomodulatory effect of hydrophilic materials is closely related to their hydration characteristics and their ability to resist non-specific binding in complex media.

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“…The initiation, maintenance, and suppression of immune responses mostly depend upon the communication occurring at the natural interfaces . The cell–cell or cell–particulate interface plays an essential role in directing the behavior of immune systems and inspire the design of nanoparticles (NPs) with immune activity . The function of NPs in tuning the immune response is determined by the physicochemical properties of the NP surfaces .…”

Section: Figurementioning

confidence: 99%

Mitigation of Inflammatory Immune Responses with Hydrophilic Nanoparticles

Li

¹

,

Xie

²

,

Yuan

³

et al. 2018

Angewandte Chemie

10

0

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While hydrophobic nanoparticles (NPs) have been long recognized to boost the immune activation, whether hydrophilic NPs modulate an immune system challenged by immune stimulators and howtheir hydrophilic properties may affect the immune response is still unclear.T oa nswer this question, three polymers,p oly(ethylene glycol) (PEG), poly-(sulfobetaine) (PSB) and poly(carboxybetaine) (PCB), which are commonly considered hydrophilic, are studied in this work. Forcomparison, nanogels with uniform sizeand homogeneous surface functionalities were made from these polymers.Peripheral blood mononuclear cells (PBMCs) stimulated by lipopolysaccharide (LPS) and an LPS-induced lung inflammation murine model were used to investigate the influence of nanogels on the immune system. Results show that the treatment of hydrophilic nanogels attenuated the immune responses elicited by LPS both in vitro and in vivo.Moreover, we found that PCB nanogels,w hichh ave the strongest hydration and the lowest non-specific protein binding,m anifested the best performance in alleviating the immune activation, followed by PSB and PEG nanogels.T his reveals that the immunomodulatory effect of hydrophilic materials is closely related to their hydration characteristics and their ability to resist non-specific binding in complex media.The initiation, maintenance,a nd suppression of immune responses mostly depend upon the communication occurring at the natural interfaces.[1] Thec ell-cell or cell-particulate interface plays an essential role in directing the behavior of immune systems and inspire the design of nanoparticles (NPs) with immune activity. [1c, 2] Thef unction of NPs in tuning the immune response is determined by the physicochemical properties of the NP surfaces. [3] It is now well known that NPs with large hydrophobic surfaces are able to trigger the initiation of innate immune responses.A ni ncrease in the hydrophobicity of NPs could even promote inflammatory outcomes including the expression of pro-inflammatory cytokines and activation of antigen-presenting cells.T his phenomenon corresponds to the classical "hyppo" model in which hydrophobic portions (hyppos) are ascribed to be integral parts of both exogenous and endogenous immune stimulators. [4] By contrast, hydrophilic nanomaterials are known to generate minimal immune reactions and cause less inflammation than their hydrophobic counterparts. [2a] Recent studies showed that PCB-uricase nanogels did not generate anti-polymer antibodies,while anti-PEG antibodies were observed after multiple injections of PEG-uricase conjugates.T hese results indicate that not all hydrophilic materials behave the same towards the immune system. Since hydrophilic materials are extensively used in nanomedicine,it is of paramount importance to understand if hydrophilic NPs can modulate an immune system challenged by immune stimulators and how hydrophilic properties may affect the immune responses.To probe the effect of surface chemistry on biological systems,inorganic NPs such as AuNPs decorated wit...

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Biomimetic and synthetic interfaces to tune immune responses (Review)

Cited by 6 publications

References 144 publications

Shape of ligand immobilized particles dominates and amplifies the macrophage cytokine response to ligands

Shape of ligand immobilized particles dominates and amplifies the macrophage cytokine response to ligands

Mitigation of Inflammatory Immune Responses with Hydrophilic Nanoparticles

Mitigation of Inflammatory Immune Responses with Hydrophilic Nanoparticles

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