An oral pH-activated “nano-bomb” carrier combined with berberine by regulating gene silencing and gut microbiota for site-specific treatment of ulcerative colitis

Yang, Mei; Yang, Chunhua; Zhang, Yujie; Yan, Xiangji; Ma, Yana; Zhang, Yuanyuan; Cao, Yameng; Xu, Qiuran; Tu, Kangsheng; Zhang, Mingzhen

doi:10.1039/d1bm01765a

Cited by 26 publications

(18 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Apart from presenting antigens, activated APCs also secrete proinflammatory cytokines, causing epithelial cell damage. [ 12 , 13 ] Together, these diverse responses promote cell apoptosis, a significant pathologic discovery in DED. Conclusively, to break DED's vicious circle in the early stages, inflammation alleviation by inhibiting the MAPK signaling pathway in both epithelium and resident immune cells is a promising strategy.…”

Section: Introductionmentioning

confidence: 99%

Anti‐Oxidative and Anti‐Inflammatory Micelles: Break the Dry Eye Vicious Cycle

Huang

et al. 2022

Advanced Science

View full text Add to dashboard Cite

Dry eye disease (DED) impacts ≈30% of the world's population and causes serious ocular discomfort and even visual impairment. Inflammation is one core cause of the DED vicious cycle, a multifactorial deterioration in DED process. However, there are also reactive oxygen species (ROS) regulating inflammation and other points in the cycle from the upstream, leading to treatment failure of current therapies merely targeting inflammation. Accordingly, the authors develop micelle‐based eye drops (more specifically p38 mitogen‐activated protein kinases (MAPK) inhibitor Losmapimod (Los)‐loaded and ROS scavenger Tempo (Tem)‐conjugated cationic polypeptide micelles, designated as MTem/Los) for safe and efficient DED management. Cationic MTem/Los improve ocular retention of conjugated water‐soluble Tem and loaded water‐insoluble Los via electrostatic interaction with negatively charged mucin on the cornea, enabling an increase in therapeutic efficiency and a decrease in dosing frequency. Mechanistically, MTem/Los effectively decrease ROS over‐production, reduce the expression of proinflammatory cytokines and chemokines, restrain macrophage proinflammatory phenotypic transformation, and inhibit cell apoptosis. Therapeutically, the dual‐functional MTem/Los suppress the inflammatory response, reverse corneal epithelial defect, save goblet cell dysfunction, and recover tear secretion, thus breaking the vicious cycle and alleviating the DED. Moreover, MTem/Los exhibit excellent biocompatibility and tolerability for potential application as a simple and rapid treatment of oxidative stress‐ and inflammation‐induced disorders, including DED.

show abstract

Section: Introductionmentioning

confidence: 99%

Anti‐Oxidative and Anti‐Inflammatory Micelles: Break the Dry Eye Vicious Cycle

Huang

et al. 2022

Advanced Science

View full text Add to dashboard Cite

show abstract

“…Of the remaining articles, 52 records were removed by reading the titles and abstracts. Finally, 28 articles were finally included after full text assessment ( Hong et al, 2012 ; Li et al, 2016a ; Li et al, 2016b ; Zhang et al, 2017 ; Cui et al, 2018 ; Jing et al, 2018 ; Li and Shen, 2018 ; Yu et al, 2018 ; Li et al, 2019a ; Li et al, 2019b ; Hui et al, 2019 ; Liao et al, 2019 ; Zhu et al, 2019 ; Jia et al, 2020a ; Li et al, 2020a ; Jia et al, 2020b ; Li et al, 2020b ; Deng et al, 2020 ; Ding et al, 2020 ; Han et al, 2020 ; Liao et al, 2020 ; Yan et al, 2020 ; Zhai et al, 2020 ; Li et al, 2021a ; Li et al, 2021b ; Jiang et al, 2021 ; Zheng et al, 2021 ; Yang et al, 2022 ). The document screening flow chart is shown in Figure 2 .…”

Section: Resultsmentioning

confidence: 99%

“…A total of 508 animals were included, including 254 in the experimental group and 254 in the model group. Animal species included BALB/c mice ( Hong et al, 2012 ; Cui et al, 2018 ; Li and Shen, 2018 ; Yu et al, 2018 ; Li et al, 2019a ; Jia et al, 2020a ; Deng et al, 2020 ; Yan et al, 2020 ; Li et al, 2021a ; Li et al, 2021b ), C57BL/6 mice ( Li et al, 2016a ; Li et al, 2016b ; Zhang et al, 2017 ; Li et al, 2019b ; Li et al, 2020a ; Li et al, 2020b ; Ding et al, 2020 ; Han et al, 2020 ; Zhai et al, 2020 ; Yang et al, 2022 ), kunming mice ( Hui et al, 2019 ), Wistar rats ( Zhu et al, 2019 ; Jia et al, 2020b ), and Sprague-Dawley rats ( Jing et al, 2018 ; Liao et al, 2019 ; Liao et al, 2020 ; Jiang et al, 2021 ). One study ( Zheng et al, 2021 ) indicated the animals were mice, instead of mentioning their specific strain.…”

Section: Resultsmentioning

confidence: 99%

“…Twenty papers used only male animals to conduct experiments ( Li et al, 2016a ; Li et al, 2016b ; Zhang et al, 2017 ; Jing et al, 2018 ; Li and Shen, 2018 ; Yu et al, 2018 ; Li et al, 2019b ; Hui et al, 2019 ; Liao et al, 2019 ; Zhu et al, 2019 ; Jia et al, 2020a ; Li et al, 2020a ; Jia et al, 2020b ; Li et al, 2020b ; Han et al, 2020 ; Liao et al, 2020 ; Yan et al, 2020 ; Zhai et al, 2020 ; Li et al, 2021a ; Li et al, 2021b ). Five papers used only females for the experiments ( Hong et al, 2012 ; Cui et al, 2018 ; Li et al, 2019a ; Ding et al, 2020 ; Yang et al, 2022 ). Three papers did not mention animal sex ( Deng et al, 2020 ; Jiang et al, 2021 ; Zheng et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacological effects of berberine on models of ulcerative colitis: A meta-analysis and systematic review of animal studies

Wei

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Berberine (BBR) is the main active constituent of the Rhizoma coptidis (Huanglian) and has multiple biological activities. Although current evidence suggests that the BBR has a multi-target effect in ulcerative colitis (UC), its action and mechanism are unclear. The purpose of this meta-analysis was to assess the pharmacological effects and potential mechanisms of BBR in UC models. Studies were searched from four databases (PubMed, Embase, Web of Science, and Cochrane Library) until March 2022. Standardized mean difference (SMD) and 95% confidence intervals (CI) were used for the adjudication of outcomes. Stata 15.0 software was used for statistical analysis. Twenty-eight publications and 29 studies involving 508 animals were included in the meta-analysis. The results showed that BBR reduced disease activity index (DAI) scores, alleviated UC-induced colon length (CL) loss, prevented weight loss, and reduced histological colitis score (HCS). Mechanistically, BBR was found to reduce myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels, reduce levels of pro-inflammatory factors interleukin-1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interferon-γ (IFN-γ) and mRNA expression of interleukin 17, increase levels of anti-inflammatory factor interleukin 10 (IL-10), and to increase levels of tight junction protein zonula occludens-1 (ZO-1) and occludin, which may involve antioxidant, anti-apoptotic, neuromodulation, anti-fibrotic, anti-inflammatory, barrier protection, and flora regulation aspects. However, additional attention should be paid to these outcomes due to the heterogeneity and methodological quality of the studies.

show abstract

“…Inflammatory bowel disease (IBD) is a chronic relapsing idiopathic inflammatory disorder of the gastrointestinal tract with an increased prevalence over the last decades. , Studies on the etiology of IBD reported the excessively produced reactive oxygen species (ROS)-induced oxidative damage and increased pro-inflammatory cytokines in the inflamed colon . For decades, nanomaterial-mediated gene therapy and antioxidant damage treatment have emerged in IBD. − Imparting gene carriers with antioxidant ability is expected to address the functional integration and simplify the synthesis process. In addition, efficient gene drug delivery and controlled release through interfacial modification of nanomaterials remain to be an urgent issue.…”

Section: Introductionmentioning

confidence: 99%

Polycatechol-Derived Mesoporous Polydopamine Nanoparticles for Combined ROS Scavenging and Gene Interference Therapy in Inflammatory Bowel Disease

Wang

Pan

et al. 2022

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

Benefiting from the evolution of nanotechnology, the combination therapy by gene interference and reactive oxygen species (ROS) scavenging are expected, which holds great potential in inflammatory bowel disease (IBD) therapy. However, the functional integration of different therapeutic modules through interface modification of gene vectors for safe and efficient treatment is urgently needed. Herein, we present a catechol chemistry-mediated core–shell nanoplatform for ROS scavenging-mediated oxidative stress alleviation and siRNA-mediated gene interference in a dextran sulfate sodium (DSS)-induced colitis model. The nanoplatform is constructed by employing mesoporous polydopamine nanoparticles (MPDA NPs) with surface modification of amines as the porous core for TNF-α-siRNA loading (31 wt %) and exerts an antioxidant function, while PDA-induced biomineralization of the calcium phosphate (CaP) coating is used as the pH-sensitive protective shell to prevent siRNA from premature release. The CaP layer degraded under weakly acidic subcellular conditions (lysosomes); thus, the synergistic integration of catechol and cation moieties on the exposed surface of MPDA resulted in an efficient lysosomal escape. Subsequently, effective ROS scavenging caused by the electron-donating ability of MPDA and efficient knocking down (40.5%) of tumor necrosis factor-α (TNF-α) via sufficient cytosolic gene delivery resulted in a synergistic anti-inflammation therapeutic effect both in vitro and in vivo. This work establishes the first paradigm of synergistic therapy in IBD by ROS scavenging and gene interference.

show abstract

An oral pH-activated “nano-bomb” carrier combined with berberine by regulating gene silencing and gut microbiota for site-specific treatment of ulcerative colitis

Abstract: Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease that features colonic epithelial barrier dysfunction and gut dysbiosis. Preclinical studies demonstrated that inhibiting the overexpression of CD98 via small...

Cited by 26 publications

References 64 publications

Anti‐Oxidative and Anti‐Inflammatory Micelles: Break the Dry Eye Vicious Cycle

Anti‐Oxidative and Anti‐Inflammatory Micelles: Break the Dry Eye Vicious Cycle

Pharmacological effects of berberine on models of ulcerative colitis: A meta-analysis and systematic review of animal studies

Polycatechol-Derived Mesoporous Polydopamine Nanoparticles for Combined ROS Scavenging and Gene Interference Therapy in Inflammatory Bowel Disease

Contact Info

Product

Resources

About