Cationic nanoparticle as an inhibitor of cell-free DNA-induced inflammation

Liang, Huiyi; Peng, Bo; Dong, Chengyan; Liu, Lixin; Mao, Jiaji; Song, Wei; Wang, Xinlu; Xu, Hanshi; Shen, Jun; Mao, Hai‐Quan; Gao, Xiaohu; Leong, Kam W.; Chen, Yongming

doi:10.1038/s41467-018-06603-5

Cited by 132 publications

(119 citation statements)

References 48 publications

(60 reference statements)

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“…Encouraged by the high NA-binding capacity and effective inflammatory inhibition of cNPs in a previous study ( 19 ), we used cNPs to interfere with the cfDNA-LL37 complex for psoriasis treatment. In particular, the excellent NA-binding capability of cNPs by charge interactions resulted in potent destruction of the NA inflammasome by forming a more compact polymer-NA complex.…”

Section: Discussionmentioning

confidence: 99%

Topical nanoparticles interfering with the DNA-LL37 complex to alleviate psoriatic inflammation in mice and monkeys

Liang

Yan

et al. 2020

Sci. Adv.

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Cell-free DNA (cfDNA) released from damaged or dead cells combines with LL37 and is converted into an immune response activator to exacerbate psoriasis. Here, we show that cationic nanoparticles (cNPs) efficiently compete for DNA from the DNA-LL37 immunocomplex and inhibit DNA-LL37-induced cell activation. Using phenotypical images, psoriasis area and severity index scoring, histology, and immunohistochemical analysis, we demonstrate that topical application of cNPs on psoriasiform skin of a mouse model relieves psoriatic symptoms. It is noteworthy that the results were confirmed in a cynomolgus monkey model. Moreover, topically administrated cNPs showed low in vivo toxicity because of their retention in skin. Mechanistic analyses of cytokine expression in the psoriatic site, cfDNA levels in circulation and inflamed skin, skin permeation, and biodistribution of cNPs also matched the therapeutic outcomes. Therefore, we present a previously unidentified strategy of nanomedicine to treat skin inflammatory diseases, which demonstrates great potential for clinical application.

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Section: Discussionmentioning

confidence: 99%

Topical nanoparticles interfering with the DNA-LL37 complex to alleviate psoriatic inflammation in mice and monkeys

Liang

Yan

et al. 2020

Sci. Adv.

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“…It is worth noting that nanoparticles can also be exploited for the removal of DAMPs such as cell-free DNA that is expelled from dying cells to ameliorate inflammatory diseases initiated by the inappropriate activation of TLR signaling. Hence, Liang et al 119 prepared cationic nanoparticles composed of the block copolymer of PLGA and poly(2-(diethylamino)ethyl methacrylate), and found that these particles had a high DNA-binding capacity. Furthermore, when injected intravenously the cationic nanoparticles could alleviate symptoms in animal models of arthritis.…”

Section: Decoding Danger At the Nanoscalementioning

confidence: 99%

Nano-bio interactions: a neutrophil-centric view

et al. 2019

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Neutrophils are key components of the innate arm of the immune system and represent the frontline of host defense against intruding pathogens. However, neutrophils can also cause damage to the host. Nanomaterials are being developed for a multitude of different purposes and these minute materials may find their way into the body through deliberate or inadvertent exposure; understanding nanomaterial interactions with the immune system is therefore of critical importance. However, whereas numerous studies have focused on macrophages, less attention is devoted to nanomaterial interactions with neutrophils, the most abundant leukocytes in the blood. We discuss the impact of engineered nanomaterials on neutrophils and how neutrophils, in turn, may digest certain carbon-based materials such as carbon nanotubes and graphene oxide. We also discuss the role of the corona of proteins adsorbed onto the surface of nanomaterials and whether nanomaterials are sensed as pathogens by cells of the immune system.

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“…Although the factors that drove persistent cellular activation in RA remain elusive, the data from animal models and clinical studies suggest that cfDNA plays a key role in driving inflammation for RA . By scavenging the cfDNA, recently we showed that polycationic nanoparticles can inhibit the persistent inflammation in RA to achieve significant symptom relief . Here we designed and synthesized a series of cationic dendronized polymers (cDenpols) to demonstrate that toxicity, NA binding capacity, and biodistribution could be balanced to achieve maximum therapeutic effect with exquisite control of the molecular structure.…”

Section: Figurementioning

confidence: 99%

Tuned Cationic Dendronized Polymer: Molecular Scavenger for Rheumatoid Arthritis Treatment

Peng

Liang

et al. 2019

Angew Chem Int Ed

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Cell‐free deoxyribonucleic acid (cfDNA) released from either dead or damaged cells serves as a key autoantigen in rheumatoid arthritis (RA). They can be recognized by nucleic acid (NA) sensors such as the toll‐like receptor (TLR), leading to activation of the innate immune system and chronic inflammation. Developed here is a cationic molecular scavenger, by screening cationic dendronized polymers, which eliminates cfDNA and inhibits TLR recognition and nucleic‐acid‐induced inflammation. The structure–property study demonstrates that toxicity, NA binding capacity, and biodistribution could be balanced to achieve maximum therapeutic effect by exquisite control of the molecular structure. In addition, the optimized cationic polymer effectively inhibited joint swelling, synovial hyperplasia, and bone destruction in collagen‐induced arthritis (CIA) rat models. The results offer support for synthetic polymers offering new paradigm in autoimmune disease treatment.

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Cationic nanoparticle as an inhibitor of cell-free DNA-induced inflammation

Cited by 132 publications

References 48 publications

Topical nanoparticles interfering with the DNA-LL37 complex to alleviate psoriatic inflammation in mice and monkeys

Topical nanoparticles interfering with the DNA-LL37 complex to alleviate psoriatic inflammation in mice and monkeys

Nano-bio interactions: a neutrophil-centric view

Tuned Cationic Dendronized Polymer: Molecular Scavenger for Rheumatoid Arthritis Treatment

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