Dual-targeting celecoxib nanoparticles protect intestinal epithelium and regulate macrophage polarization for ulcerative colitis treatment

Chen, Ruijie; Lin, Xinlu; Wang, Qian; An, Xingsi; Zhao, Xinyu; Lin, Yujie; Sun, Tuyue; Yan, Chenyang; Cai, Aimin; Cao, Weilan; Zhang, Youting; Yao, Qing; Kou, Longfa

doi:10.1016/j.cej.2022.139445

Cited by 24 publications

(6 citation statements)

References 53 publications

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“…MPO, an enzyme often implicated in the inflammatory response, serves as an additional index of cellular processes relevant to the pulmonary tissue’s physiological state under the studied conditions. Correspondingly, augmented MPO levels observed in the disease model group were reduced upon treatment with various BRNP formulations, aligning with prior reports that indicate an intrinsic antiinflammatory capacity of BR-based nanoparticles. − Taken collectively, these results implied that while LPS exposure could precipitate oxidative stress and inflammation, the administration of BRNP might significantly amend the redox and inflammatory state toward homeostasis.…”

Section: Resultssupporting

confidence: 88%

Bilirubin Nanoparticles Alleviate Sepsis-Induced Acute Lung Injury by Protecting Pulmonary Endothelia Glycocalyx and Reducing Inflammation

Xia,

Sun,

Zhao

et al. 2024

ACS Appl. Nano Mater.

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Acute lung injury (ALI) remains one of the most common complications of sepsis. Although many potential effective pharmacologic and ventilatory treatment strategies have been reported, there is still a lack of effective means of treatment of sepsis-induced ALI in the clinic. The aim of this study is to develop an easy-made endogenous bilirubin nanoparticle (BRNP) that could treat sepsis-induced ALI and investigate its underlying therapeutic mechanism. We prepared BRNP by bilirubin (BR) selfassembly and bovine serum albumin (BSA) coating with a simple one-pot nanoprecipitation method. BRNP holds good physical stability and could release BR in a sustained manner in a neutral medium but initiate a burst release in either acidic or oxidative conditions. In a sepsis murine model, BRNP could substantially alleviate the sepsis-induced lung injury, as evidenced by reduced histopathological changes of lung tissues and also reduced inflammation development. Mechanically, BRNP could alleviate the glycocalyx damage, inhibit the NF-κB pathway, and reduce proinflammatory factor release in vivo. This study provides a simple and robust BRNP to treat sepsis-induced ALI, which may pave the way to design multifunctional nanomedicine for clinical translation.

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Section: Resultssupporting

confidence: 88%

Bilirubin Nanoparticles Alleviate Sepsis-Induced Acute Lung Injury by Protecting Pulmonary Endothelia Glycocalyx and Reducing Inflammation

Xia,

Sun,

Zhao

et al. 2024

ACS Appl. Nano Mater.

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“…Further experiments revealed that such beneficial effects were associated with the modulation of intestinal epithelial/stem cells regeneration and decreasing of angiogenesis and inflammation. In particular, this is also the first demonstration that HA-PLGAbilirubin treatment can ameliorate DSS-induced colitis by modulating colonic epithelial/stem cells regeneration, which extends our knowledge on the therapeutic mechanisms of bilirubin [51][52][53]. By shedding light on this innovative area of research, our findings may pave the way for the development of bilirubin for the treatment of chronic inflammatory conditions.…”

Section: Discussionsupporting

confidence: 63%

Targeted modulation of intestinal epithelial regeneration and immune response in ulcerative colitis using dual-targeting bilirubin nanoparticles

Zhuo,

Guo,

Luo

et al. 2024

Theranostics

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Rationale: The therapeutic benefits of bilirubin in the treatment of ulcerative colitis (UC) are considerable, whereas the underlying mechanism of bilirubin on UC remains unclear remains unexplored. In addition, the weak hydrophilicity and toxicity have limited its translational applications. Methods: We have developed a colon dual-targeting nanoparticle, for orally delivering bilirubin through hydrogel encapsulation of hyaluronic acid (HA)-modified poly (lactic-co-glycolic acid) (PLGA) nanoparticles (HA-PLGA Bilirubin ). Confocal microscopy and in vivo imaging were used to evaluate the uptake and the targeted property of HA-PLGA Bilirubin in UC. Immunohistochemistry, immunofluorescence, and transcriptomic analyses were applied to examine the therapeutic effect and potential mechanism of HA-PLGA Bilirubin in UC. Results: Our results indicated that HA-PLGA bilirubin can significantly enhance the release of bilirubin at simulated intestinal pH and demonstrate higher cellular uptake in inflammatory macrophages. Moreover, in vivo biodistribution studies revealed high uptake and retention of HA-PLGA bilirubin in inflamed colon tissue of UC mouse model, resulting in effective recovery of intestinal morphology and barrier function. Importantly, HA-PLGA bilirubin exerted potent therapeutic efficacy against ulcerative colitis through modulating the intestinal epithelial/stem cells regeneration, and the improvement of angiogenesis and inflammation. Furthermore, genome-wide RNA-seq analysis revealed transcriptional reprogramming of immune response genes in colon tissue upon HA-PLGA bilirubin treatment in UC mouse model. Conclusion: Overall, our work provides an efficient colon targeted drug delivery system to potentiate the treatment of ulcerative colitis via modulating intestinal epithelium regeneration and immune response in ulcerative colitis.

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“…The progression of colon inflammation is greatly influenced by macrophage polarization; M1/M2-polarized macrophages are responsible for the secretion of pro-inflammatory factors and anti-inflammatory factors, respectively. 53 In order to study whether the influence of NEFY on inflammatory factors is related to the M1/M2 polarization of macrophages, we observed the distribution of M1 and M2 macrophages in colon tissues by double immunofluorescence. CD86 and CD163 were used as molecular markers of M1 and M2 positive macrophages, respectively.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Highly Effective Nobiletin–MPN in Yeast Microcapsules for Targeted Modulation of Oxidative Stress, NLRP3 Inflammasome Activation, and Immune Responses in Ulcerative Colitis

Yang,

Xia,

et al. 2024

J. Agric. Food Chem.

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Inflammatory bowel disease (IBD) etiology is intricately linked to oxidative stress and inflammasome activation. Natural antioxidant nobiletin (NOB) contains excellent anti-inflammatory properties in alleviating intestinal injury. However, the insufficient water solubility and low bioavailability restrict its oral intervention for IBD. Herein, we constructed a highly efficient NOB-loaded yeast microcapsule (YM, NEFY) exhibiting marked therapeutic efficacy for dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) at a low oral dose of NOB (20 mg/kg). We utilized the metal polyphenol network (MPN) formed by selfassembly of epigallocatechin gallate (EGCG) and FeCl 3 as the intermediate carrier to improve the encapsulation efficiency (EE) of NOB by 4.2 times. These microcapsules effectively alleviated the inflammatory reaction and oxidative stress of RAW264.7 macrophages induced by lipopolysaccharide (LPS). In vivo, NEFY with biocompatibility enabled the intestinal enrichment of NOB through controlled gastrointestinal release and macrophage targeting. In addition, NEFY could inhibit NLRP3 inflammasome and balance the macrophage polarization, which favors the complete intestinal mucosal barrier and recovery of colitis. Based on the oral targeted delivery platform of YM, this work proposes a novel strategy for developing and utilizing the natural flavone NOB to intervene in intestinal inflammation-related diseases.

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Dual-targeting celecoxib nanoparticles protect intestinal epithelium and regulate macrophage polarization for ulcerative colitis treatment

Cited by 24 publications

References 53 publications

Bilirubin Nanoparticles Alleviate Sepsis-Induced Acute Lung Injury by Protecting Pulmonary Endothelia Glycocalyx and Reducing Inflammation

Bilirubin Nanoparticles Alleviate Sepsis-Induced Acute Lung Injury by Protecting Pulmonary Endothelia Glycocalyx and Reducing Inflammation

Targeted modulation of intestinal epithelial regeneration and immune response in ulcerative colitis using dual-targeting bilirubin nanoparticles

Highly Effective Nobiletin–MPN in Yeast Microcapsules for Targeted Modulation of Oxidative Stress, NLRP3 Inflammasome Activation, and Immune Responses in Ulcerative Colitis

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