Bilirubin nanomedicine alleviates psoriatic skin inflammation by reducing oxidative stress and suppressing pathogenic signaling

Keum, Hyeongseop; Kim, Tae Woo; Kim, Yujin; Seo, Changjin; Son, Youngju; Kim, Jinjoo; Kim, Do-Hyeon; Jung, Woong; Whang, Chang-Hee; Jon, Sangyong

doi:10.1016/j.jconrel.2020.07.015

Cited by 56 publications

(43 citation statements)

References 41 publications

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“…BRNPs were prepared from self-assembly of hydrophilic poly(ethylene glycol)-modified bilirubin (PEG-BR) in an aqueous solution ( Fig. 1 A) [ 15 ]. The size of BRNPs measured by transmission electron microscopy (TEM) ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…S5B ). To date, however, no such adverse effects have been observed for BRNPs in various mouse models [ [11] , [12] , [13] , [14] , [15] , [16] ]. Collectively, these findings indicate that BRNPs are less toxic and constitute a far superior therapeutic compared with native bilirubin.…”

Section: Resultsmentioning

confidence: 99%

“…PEGylated bilirubin (PEG-BR) was synthesized as previously described [ 15 ]. Briefly, bilirubin (BR) was purchased from Tokyo Chemical Industry, Co. (Tokyo, Japan) and amine-functionalized methoxy-poly(ethylene)glycol (mPEG 2K –NH 2 ; Mw ∼2000) was purchased from NANOCS (New York, NY, USA).…”

Section: Methodsmentioning

confidence: 99%

“…We recently demonstrated that bilirubin nanoparticles (BRNPs), comprising the potent endogenous antioxidant molecule, bilirubin, exert significant anti-inflammatory efficacy against various oxidative stress-associated diseases, including inflammatory bowel disease (IBD), hepatic ischemia-reperfusion injury (IRI), allergic lung inflammation, islet xenotransplantation, psoriasis, and experimental autoimmune encephalomyelitis (EAE), by effectively scavenging excess ROS upon an inflammatory trigger [ [11] , [12] , [13] , [14] , [15] , [16] ]. Encouraged by these previous studies, we hypothesized that BRNPs could successfully reduce exaggerated ROS levels following lung parenchyma injury and hinder propagation of the pathogenic cascade.…”

Section: Introductionmentioning

confidence: 99%

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A bilirubin-derived nanomedicine attenuates the pathological cascade of pulmonary fibrosis

Keum

Kim

et al. 2021

Biomaterials

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Pulmonary fibrosis is an irreparable and life-threatening disease with only limited therapeutic options. The recent outbreak of COVID-19 has caused a sharp rise in the incidence of pulmonary fibrosis owing to SARS-CoV-2 infection-mediated acute respiratory distress syndrome (ARDS). The considerable oxidative damage caused by locally infiltrated immune cells plays a crucial role in ARDS, suggesting the potential use of antioxidative therapeutics. Here, we report the therapeutic potential of nanoparticles derived from the endogenous antioxidant and anti-inflammatory bile acid, bilirubin (BRNPs), in treating pulmonary fibrosis in a bleomycin-induced mouse model of the disease. Our results demonstrate that BRNPs can effectively reduce clinical signs in mice, as shown by histological, disease index evaluations, and detection of biomarkers. Our findings suggest that BRNPs, with their potent antioxidant and anti-inflammatory effects, long blood circulation half-life, and preferential accumulation at the inflamed site, are potentially a viable clinical option for preventing Covid-19 infection-associated pulmonary fibrosis.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A bilirubin-derived nanomedicine attenuates the pathological cascade of pulmonary fibrosis

Keum

Kim

et al. 2021

Biomaterials

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“…Bilirubin, as the final product of the metabolism pathway of heme, is a potent endogenous antioxidant capable of scavenging various ROS and thereby protecting cells from oxidative stress-mediated damage. Jon group originally explored anti-inflammatory activity of nanoparticles self-assembled from PEGylated bilirubin for the treatment of colitis, asthma, and psoriasis, by effectively diminishing ROS and modulating the immune system [ 74 – 76 ]. Typically, in a mouse model of ulcerative colitis, intravenous injection of nanoparticles of PEGylated bilirubin exhibited preferred accumulation at the sites of inflammation and remarkably inhibited the progression of inflammation process in the colon [ 74 ].…”

Section: Inflammation-responsive Ddssmentioning

confidence: 99%

Inflammation-responsive delivery systems for the treatment of chronic inflammatory diseases

Deng

Liu

2021

Drug Deliv. and Transl. Res.

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Graphical abstract Inflammation is the biological response of immune system to protect living organisms from injurious factors. However, excessive and uncontrolled inflammation is implicated in a variety of devastating chronic diseases including atherosclerosis, inflammatory bowel disease (IBD), and rheumatoid arthritis (RA). Improved understanding of inflammatory response has unveiled a rich assortment of anti-inflammatory therapeutics for the treatment and management of relevant chronic diseases. Notwithstanding these successes, clinical outcomes are variable among patients and serious adverse effects are often observed. Moreover, there exist some limitations for clinical anti-inflammatory therapeutics such as aqueous insolubility, low bioavailability, off-target effects, and poor accessibility to subcellular compartments. To address these challenges, the rational design of inflammation-specific drug delivery systems (DDSs) holds significant promise. Moreover, as compared to normal tissues, inflamed tissue-associated pathological milieu (e.g., oxidative stress, acidic pH, and overexpressed enzymes) provides vital biochemical stimuli for triggered delivery of anti-inflammatory agents in a spatiotemporally controlled manner. In this review, we summarize recent advances in the development of anti-inflammatory DDSs with built-in pathological inflammation-specific responsiveness for the treatment of chronic inflammatory diseases.

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Biliverdin and Bilirubin as Parallel Products of CO Formation

Vı́tek

2022

Carbon Monoxide in Drug Discovery

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Bilirubin nanomedicine alleviates psoriatic skin inflammation by reducing oxidative stress and suppressing pathogenic signaling

Cited by 56 publications

References 41 publications

A bilirubin-derived nanomedicine attenuates the pathological cascade of pulmonary fibrosis

A bilirubin-derived nanomedicine attenuates the pathological cascade of pulmonary fibrosis

Inflammation-responsive delivery systems for the treatment of chronic inflammatory diseases

Biliverdin and Bilirubin as Parallel Products of CO Formation

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