Synthetic high-density lipoprotein-like nanoparticles potently inhibit cell signaling and production of inflammatory mediators induced by lipopolysaccharide binding Toll-like receptor 4

Foit, Linda; Thaxton, C. Shad

doi:10.1016/j.biomaterials.2016.05.021

Cited by 55 publications

(42 citation statements)

References 55 publications

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“…This nanoparticle (NP) inhibitor was found to suppress LPS-induced MyD88-dependent NF-κB activation and inhibit subsequent cytokines production in mouse macrophages (Babazada et al, 2014b). The high-density lipoprotein (HDL)-like nanoparticle (HDL-like NP) was developed as a TLR4 antagonist by sequestering LPS (Foit & Thaxton, 2016) and has been applied to reduce LPS-induced inflammation in vivo (Guo et al, 2013). Gold nanoparticles (GNPs) have caught much attention in nanomedicine (Pedrosa et al, 2015).…”

Section: New Emerging Nano-inhibitorsmentioning

confidence: 99%

Toll-like receptors activation, signaling, and targeting: an overview

2019

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Background: Toll-like receptors (TLRs) are an important family of receptors that constitute the first line of defense system against microbes. They can recognize both invading pathogens and endogenous danger molecules released from dying cells and damaged tissues and play a key role in linking innate and adaptive immunity. TLRs are widely distributed in both immune and other body cells. The expressions and locations of TLRs are regulated in response to specific molecules derived from pathogens or damaged host cells. The binding of ligands to TLR activates specific intracellular signaling cascades that initiate host defense reactions. Such binding is liganddependent and cell type-dependent and leads to production of pro-inflammatory cytokines and type 1 interferon. TLR-dependent signaling pathways are tightly increased during innate immune responses by a variety of negative regulators. Overactivation of TLRs can ultimately lead to disruption of immune homeostasis and thus increase the risk for inflammatory diseases and autoimmune disorders. Antagonists/inhibitors targeting the TLR signaling pathways have emerged as novel therapeutics to treat these diseases. Aim of work: The present review summarizes the structure, characterizations, and signaling of TLRs and their regulators, as well as describes the implication of TLRs in many diseases with a brief idea about the inhibitors that target TLR signaling pathways. Conclusion: We conclude that TLRs are the main elements of our immune system, and they should be maintained functioning to keep the integrity of innate immunity. Targeting of TLR signaling represents a new challenge for treatment of many diseases.

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Section: New Emerging Nano-inhibitorsmentioning

confidence: 99%

Toll-like receptors activation, signaling, and targeting: an overview

2019

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“…Another novel nanodevice, the high-density lipoprotein (HDL)-like nanoparticle (HDL-like NP), was developed as a TLR4 antagonist by sequestering LPS (Foit and Thaxton, 2016). HDL has been known to naturally bind to and neutralize LPS (Brandenburg et al, 2002), and has been applied to reduce LPS-induced inflammation in vivo (Pajkrt et al, 1996; Guo et al, 2013).…”

Section: Toll-like Receptor Antagonists/inhibitors and Their Clinicalmentioning

confidence: 99%

“…HDL has been known to naturally bind to and neutralize LPS (Brandenburg et al, 2002), and has been applied to reduce LPS-induced inflammation in vivo (Pajkrt et al, 1996; Guo et al, 2013). The HDL-like NP was designed with a gold NP core and a HDL coating, where the lipid components of HDL can be modified (Foit and Thaxton, 2016). Through screening five variants of the lipid coatings, one HDL-like NP was identified to be able to potently inhibit TLR4 signaling triggered by various sources of LPS and Gram-negative bacteria on human cell lines and PBMC.…”

Section: Toll-like Receptor Antagonists/inhibitors and Their Clinicalmentioning

confidence: 99%

Inhibition of Toll-Like Receptor Signaling as a Promising Therapy for Inflammatory Diseases: A Journey from Molecular to Nano Therapeutics

et al. 2017

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The recognition of invading pathogens and endogenous molecules from damaged tissues by toll-like receptors (TLRs) triggers protective self-defense mechanisms. However, excessive TLR activation disrupts the immune homeostasis by sustained pro-inflammatory cytokines and chemokines production and consequently contributes to the development of many inflammatory and autoimmune diseases, such as systemic lupus erythematosus (SLE), infection-associated sepsis, atherosclerosis, and asthma. Therefore, inhibitors/antagonists targeting TLR signals may be beneficial to treat these disorders. In this article, we first briefly summarize the pathophysiological role of TLRs in the inflammatory diseases. We then focus on reviewing the current knowledge in both preclinical and clinical studies of various TLR antagonists/inhibitors for the prevention and treatment of inflammatory diseases. These compounds range from conventional small molecules to therapeutic biologics and nanodevices. In particular, nanodevices are emerging as a new class of potent TLR inhibitors for their unique properties in desired bio-distribution, sustained circulation, and preferred pharmacodynamic and pharmacokinetic profiles. More interestingly, the inhibitory activity of these nanodevices can be regulated through precise nano-functionalization, making them the next generation therapeutics or “nano-drugs.” Although, significant efforts have been made in developing different kinds of new TLR inhibitors/antagonists, only limited numbers of them have undergone clinical trials, and none have been approved for clinical uses to date. Nevertheless, these findings and continuous studies of TLR inhibition highlight the pharmacological regulation of TLR signaling, especially on multiple TLR pathways, as future promising therapeutic strategy for various inflammatory and autoimmune diseases.

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“…Gamazo et al demonstrated that poly (methyl vinyl ether-co-maleic anhydride) NPs (PVMA) act as agonists of TLR2 and TLR4, and highly activated complement activation by stable binding to C3b [69]. 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].…”

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

207

131

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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.

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Synthetic high-density lipoprotein-like nanoparticles potently inhibit cell signaling and production of inflammatory mediators induced by lipopolysaccharide binding Toll-like receptor 4

Cited by 55 publications

References 55 publications

Toll-like receptors activation, signaling, and targeting: an overview

Toll-like receptors activation, signaling, and targeting: an overview

Inhibition of Toll-Like Receptor Signaling as a Promising Therapy for Inflammatory Diseases: A Journey from Molecular to Nano Therapeutics

Effects of engineered nanoparticles on the innate immune system

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