Bilirubin nanomedicine ameliorates the progression of experimental autoimmune encephalomyelitis by modulating dendritic cells

Kim, Tae Woo; Kim, Yujin; Jung, Woong; Kim, Dong Eon; Keum, Hyeongseop; Son, Youngju; Jon, Sangyong

doi:10.1016/j.jconrel.2021.01.019

Cited by 37 publications

(28 citation statements)

References 54 publications

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“…Because BRNPs composed of PEGylated bilirubin have a much longer blood circulation time and higher colloidal stability than the hydrophobic small molecule, unconjugated bilirubin (UCB), the former nanomedicine is predicted to exhibit better therapeutic efficacy than the latter [ [12] , [13] , [14] , 16 ]. To test this, we intravenously injected either BRNPs (20 mg/kg; equivalent to 4.64 mg UCB/kg) or an equivalent dose of UCB (4.64 mg/kg) into bleomycin-induced pulmonary fibrosis mice.…”

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%

“…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: 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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“…Bi inhibits NOX-related ROS production and TLR4-mediated LPS inflammatory response by targeting the redox-sensitive transcription factor hypoxia inducible factor-1α (HIF-1α) [ 95 ]. Thus, Bi NPs exhibit potential for use as nanomedicines aimed at treating various inflammatory diseases [ 96 ], including ulcerative colitis [ 97 , 98 ], hepatic I/R injury [ 99 ], pulmonary fibrosis (PF) [ 100 ], AKI [ 101 ], and multiple sclerosis [ 102 ]. The latest eruption of COVID-19 had resulted in PF due to the acute respiratory distress syndrome (ARDS), and one of the key roles in ARDS was oxidative damage caused by local infiltration of immune cell.…”

Section: Ros-scavenging Nanomaterials That Promote Oxidative Damage Repair and Mechanisms Governing This Repairmentioning

confidence: 99%

Reactive-oxygen-species-scavenging nanomaterials for resolving inflammation

Huang

Zheng

et al. 2021

Materials Today Bio

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Reactive oxygen species (ROS) mediate multiple physiological functions; however, the over-accumulation of ROS causes premature aging and/or death and is associated with various inflammatory conditions. Nevertheless, there are limited clinical treatment options that are currently available. The good news is that owing to the considerable advances in nanoscience, multiple types of nanomaterials with unique ROS-scavenging abilities that influence the temporospatial dynamic behaviors of ROS in biological systems have been developed. This has led to the emergence of next-generation nanomaterial-controlled strategies aimed at ameliorating ROS-related inflammatory conditions. Accordingly, herein we reviewed recent progress in research on nanotherapy based on ROS scavenging. The underlying mechanisms of the employed nanomaterials are emphasized. Furthermore, important issues in developing cross-disciplinary nanomedicine-based strategies for ROS-based inflammatory conditions are discussed. Our review of this increasing interdisciplinary field will benefit ongoing studies and clinical applications of nanomedicine based on ROS scavenging.

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“…10 Recent studies have shown that BR exert powerful antiinflammatory actions against various oxidative stressassociated diseases, including experimental autoimmune encephalomyelitis, inflammatory bowel disease, hepatic ischemia-reperfusion injury, pulmonary fibrosis, and aluminduced peritonitis. [11][12][13][14][15] Other reports have confirmed that physiological concentrations of BR regulate inflammation by inhibiting nuclear factor kappa-B (NF-κB) and inflammasome activation. 16 In addition, previous studies in our laboratory showed that BR could modulate macrophages toward the M2-type and enhance the therapeutic effect of islet transplantation in diabetes mellitus.…”

Section: Introductionmentioning

confidence: 98%

Protective Effects of Chitosan-Bilirubin Nanoparticles Against Ethanol-Induced Gastric Ulcers

Huang¹,

Shi²,

Wang³

et al. 2021

IJN

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Gastric ulcers (GU) are a disease of the gastrointestinal tract that can be caused by excessive alcohol consumption and heavy use of nonsteroidal anti-inflammatory drugs. GU manifests predominantly as pathological damage, such as extensive inflammatory erosion and superficial bleeding of the gastric mucosa. Oxidative stress damage and the inflammatory response are now considered important predisposing factors for GU, suggesting that antioxidant and anti-inflammatory drugs could be treatments for GU. Nanoparticle drug carriers offer many advantages over conventional drugs, such as improved drug efficiency, increased drug stability, and increased half-life. Methods: We designed chitosan-bilirubin conjugate (CS-BR) nanoparticles and assessed the anti-inflammatory and antioxidant abilities of CS-BR in gastric epithelial cells. Then, we evaluated the intragastric retention time and the anti-ulcer effects of CS-BR in vivo. Results:The in vitro data showed that CS-BR nanoparticles protect gastric epithelial cells against oxidative/inflammatory injury. The in vivo study demonstrated that CS-BR nanoparticles accumulate permanently in the stomach and exert powerful antioxidant and antiinflammatory effects against GU. Conclusion:This study applied bilirubin to the treatment of GU and confirmed that CS-BR nanoparticles are effective at alleviating acute GU in an experimental model. The findings provide innovative ideas for prophylaxis against or treatment of GU.

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Bilirubin nanomedicine ameliorates the progression of experimental autoimmune encephalomyelitis by modulating dendritic cells

Cited by 37 publications

References 54 publications

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

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

Reactive-oxygen-species-scavenging nanomaterials for resolving inflammation

Protective Effects of Chitosan-Bilirubin Nanoparticles Against Ethanol-Induced Gastric Ulcers

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