CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Mengyuan Qian,Min Ge,Shanshan Liu,Xin Wen,Ning Liu,Qianqian Wang,Jiaxu Cao,Xiuyan Jiang,Yan Zhang,Jun Yang,Lingyun Sun
Inflammatory bowel disease (IBD) is an incurable condition driven by chronic inflammatory dysregulation. Human mesenchymal stem cells (hMSCs) offer therapeutic promise, but limited persistence and functional heterogeneity constrain their clinical efficacy. Here, we present a bio-inspired priming platform built on poly(lactic- co -glycolic acid)/chitosan-heparin microparticles, engineered to display E/N-cadherin motifs and to enable controlled interleukin-1β release through PLGA biodegradation. These functionalized microparticles (hE/N-cad@P/C-h-IL-1β) assemble with hMSCs into hybrid aggregates that enhance cell survival under stress and improve adaptability to microenvironment cues. The priming process upregulates endogenous cadherin expression and modulates AKT/STAT signaling, conferring stimulus- and dose-responsive immune activity. In vitro , hybrid aggregates polarize macrophages toward an anti-inflammatory phenotype, expand regulatory T cells, and suppress pathogenic lymphocyte activation. In a dextran sulfate sodium (DSS) colitis model, intraperitoneal delivery of hybrid aggregates restores intestinal immune homeostasis, accelerates epithelial repair, and reduces disease severity to near baseline within fourteen days. By integrating cell-adhesive and cytokine signals within a modular platform, this strategy overcomes critical translational barriers in hMSC therapy and provides a blueprint for precisely targeted treatment of IBD and related inflammatory disorders.
研究领域:
再生医学
·
免疫学
·
生物材料
·
干细胞治疗
·
炎症性疾病
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Jiahu Yao,Yang Yang,Hu Zhao,Chuanming Wang,Liang Jin,Tengyun Long,Wei Huang,Xiang Zhan,Xin Li,Xin Chen,Jinhu Xie,Bin Wu,Chuansi Wang,Liling Huang,Hongnian Pan,Xuan Nie,Changjun Yu,Wei Chen
The accumulation of reactive oxygen species (ROS) within colonic tissue represents a critical factor in the pathogenesis of inflammatory bowel disease (IBD). The application of antioxidant therapy utilizing artificial nanozymes has emerged as an effective strategy for the management of IBD. Nevertheless, current nanozymes exhibit limitations in stability, tissue compatibility, and systemic toxicity, which constrain their applicability within the biomedical domain. Herein, we designed a biocompatible colon-targeted integrated therapeutic system (BiOSe-RA@FP), the core of which is Bi 2 O 2 Se (BiOSe) nanosheets encapsulating natural plant rosmarinic acid (RA), enclosed within pH-responsive enteric hydrogel microspheres (FP). This system ensures targeted delivery of BiOSe-RA to the inflamed colon and prolongs its local retention time. BiOSe-RA fully exerts the activities of superoxide dismutase (SOD) and catalase (CAT) in the colon, effectively removing ROS (·OH, ·O 2 − , and H 2 O 2 ). Concurrently, BiOSe-RA exerts excellent anti-inflammatory activities in the colon, which could inhibit the secretion of inflammatory factors, and induce macrophages to polarize the M2 type. The ultimate effect is to preserve the integrity of the intestinal epithelial mucosal barrier and restore microbial homeostasis in the colon by mitigating intestinal oxidative stress and ameliorating the inflammatory microenvironment. The constructed BiOSe-RA@FP could regulate intestinal microbial community disorders, providing a safe and effective new solution for the treatment of IBD.
研究领域:
纳米技术
·
药学
·
胃肠病学
·
免疫学
·
微生物学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Yifan Cui,Dezhi Yang,Qiulan Li,Zhongmei Peng,Zitao Zhong,Yuzhu Song,Qinqin Han,Yaling Yang
Nanozyme-mediated antioxidative therapy is a promising star for treating a myriad of important diseases through eliminating excessive reactive oxygen species (ROS) such as O2·– and H2O2, a critical mechanism for inflammatory bowel disease (IBD). This work provides a high biocompatibility iodine–copper–zinc covalent doped carbon dots (Cu,Zn,I-CDs) with the catalase (CAT)-, superoxide dismutase (SOD)- and glutathione peroxidase (GPx)-like catalytic activities for treating ulcerative colitis (UC) by scavenging overproduced ROS. We found that I dopant aids in counteracting the positive charge at Cu,Zn dopants brought on by low pH, enabling Cu,Zn,I-CDs to process strong triple antioxidant nanozyme activities rather than Cu,Zn-CDs. Vitro experiments displayed that the Cu,Zn,I-CDs could scavenge the excessive ROS to protect cellular against oxidative stress and reduce the expression of proinflammatory cytokines, such as TNF-α, IL-1β, and IL-6. In sodium dextran sulfate (DSS)-induced colitis mice models, Cu,Zn,I-CDs with excellent biocompatibility could effectively relieve the inflammation of the colon, containing the reduction of the colon length, the damaged epithelium, the infiltration of inflammatory cells, and upregulation of antioxidant genes. Therefore, the therapy of Cu,Zn,I-CD antioxidant nanozymes is an effective approach and provides a novel strategy for UC treatment.
研究领域:
纳米技术
·
药学
·
医学研究
·
生物化学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Therapeutics
·
2024
·Vol. 7
·期 11
·2400275
·
IF 3.7
Yao Yao,Binqing Xue,Duncan James Lessing,Weihua Chu
Alterations in the intestinal microenvironment, including increased levels of reactive oxygen species (ROS), abnormalities in intestinal mucosal immune regulation, and dysbiosis of the intestinal microbiota, are crucial to the development of inflammatory bowel disease (IBD). Herein, an oral colon-targeting Se-Probiotic@Alginate bead (BLSe) with ROS-scavenging ability and gut immune-microbiota microenvironment remodeling ability is developed using alginate as the primary outer shell encapsulated with probiotics Bacillus licheniformis (BL) and selenium nanoparticles stabilized by yeast glucan (SeNPs). In vitro studies have shown that SeNPs possess antioxidant activity and BLSe exhibits excellent stability in gastric fluids and are released in intestinal fluids. In vivo studies have also shown that BLSe significantly alleviated dextran sulphate sodium (DSS)-induced colitis in mice by inhibiting colon shortening, enhancing antioxidant activity, reducing pro-inflammatory cytokine secretion, and protecting the intestinal mucosal barrier. 16S ribosomal RNA sequencing shows that BLSe can remodel the composition of the gut microbiota by improving bacterial diversity and restoring the relative abundance of beneficial bacteria in the colon. Overall, this study advances a promising probiotic-based nanomedicine for managing IBD.
研究领域:
药学
·
免疫学
·
微生物学
·
胃肠病学
✓ 已验证
产品关联
DOI
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-18
·
IF 14.7
Tang Xudong,Shang Yangyang,Yang Hong,Song Yalan,Li Shan,Qin Yusi,Song Jingyi,Chen Kang,Liu Yang,Zhang Dinglin,Chen Lei
The PD-1/PD-L1 pathway in mucosal immunity is currently actively explored and considered as a target for inflammatory bowel disease (IBD) treatment. However, systemic PD-L1 administration may cause unpredictable adverse effects due to immunosuppression. Here we show that reactive oxygen species (ROS)-responsive nanoparticles enhance the efficacy and safety of PD-L1 in a mouse colitis model. The nanoparticles control the accumulation and release of PD-L1 fused to Fc (PD-L1-Fc) at inflammatory sites in the colon. The nanotherapeutics shows superiority in alleviating inflammatory symptoms over systemic PD-L1-Fc administration and mitigates the adverse effects of PD-L1-Fc administration. The nanoparticles-formulated PD-L1-Fc affects production of proinflammatory and anti-inflammatory cytokines, attenuates the infiltration of macrophages, neutrophils, and dendritic cells, increases the frequencies of Treg, Th1 and Tfh cells, reshapes the gut microbiota composition; and increases short-chain fatty acid production. In summary, PD-L1-Fc-decorated nanoparticles may provide an effective and safe strategy for the targeted treatment of IBD.
研究领域:
药理学
·
免疫学
·
纳米技术
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2022
·
IF 18.027
Chengke Zhao,Jiali Yang,Mingfeng Chen,Wenjun Chen,Xinyuan Yang,Heng Ye,Liying Wang,Yong Wang,Jinjin Shi,Fengxia Yue,Xing Ma
Oral drug delivery is a common route for management of inflammatory bowel disease (IBD) but suffers from low bioavailability and systemic side effects during passage through the alimentary canal. Here, we present a therapeutic nano reagent of a ferulic acid-derived lignin nanoparticle (FALNP). We showed that FALNP with favorable antioxidant activity can regulate IBD. More importantly, the intestinal pH-responsive degradability of FALNP allows it to withstand the harsh gastric acid environment, bypass physiological barriers, and target the intestine for gastrointestinal delivery. In vivo experiments showed that oral administration of FALNP markedly relieved pathological symptoms in a mouse model of acute colitis by reducing oxidative stress and regulating the gut microbiome. By integrating anti-inflammatory medicine, FALNP also can be used as a bioactive carrier to exert a potent synergistic therapeutic effect. In addition to colitis, FALNP can be readily adaptable for use as a carrier platform for therapy of many other intestinal diseases.
研究领域:
药学
·
纳米技术
·
生物医学工程
·
胃肠病学
·
药物递送系统
·
治疗学
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Jinpeng Yao,Yu Chen,Liang Zhang,Yuancun Cheng,Zheng Chen,Yanhui Zhang,Xiaoyi Zheng,Yanwei Lv,Shige Wang,Zhaoshen Li,Jiulong Zhao
The clinical treatment of inflammatory bowel disease (IBD) is challenging. We developed copper sulfate (CuS)/disulfiram (DSF)/methacrylic acid-ethyl acrylate copolymer (EL)/polyvinylpyrrolidone (PVP) nanoplatform (CuS/DSF/EL/PVP) and evaluated its efficiency for treating IBD. After oral administration, the pH-sensitive EL protected the CuS/DSF/EL/PVP against degradation by acidic gastric juices. Once the colon was reached, EL was dissolved, releasing DSF and Cu 2+ . Further, the main in vivo metabolite of DSF can bind to Cu 2+ and form copper (II) N, N-diethyldithiocarbamate (CuET), which significantly alleviated acute colitis in mice. Notably, CuS/DSF/EL/PVP outperformed CuS/EL/PVP and DSF/EL/PVP nanoplatforms in reducing colonic pathology and improving the secretion of inflammation-related cytokines (such as IL-4 and IL-10) in the colonic mucosa. RNA-seq analysis revealed that the nanoplatform reduced colonic inflammation and promoted intestinal mucosal repair by upregulating C-type lectin receptor (CLR)-related genes and signaling pathways. Furthermore, CuS/DSF/EL/PVP showed potential for improving colitis Th1/Th17 cells through innate immunity stimulation, down-regulation of inflammatory cytokines, and upregulation of anti-inflammatory cytokines. Additionally, the intervention with CuS/DSF/EL/PVP led to increased intestinal flora diversity, decreased Escherichia–Shigella abundance, and elevated levels of short-chain fatty acid (SCFA)-producing bacteria Prevotella, Lactobacillus , and Bifidobacterium , indicating their potential to modulate the dysregulated intestinal flora and suppress inflammation. Statement of Significance Our study introduces the CuS/DSF/EL/PVP nanoplatform as a therapeutic strategy for treating inflammatory bowel disease (IBD). This approach demonstrates significant efficacy in targeting the colon and alleviating acute colitis in mice. It uniquely modulates gut immunity and microbiota, exhibiting a notable impact on inflammation-related cytokines and promoting intestinal mucosal repair. The nanoplatform's ability to regulate gut flora diversity, combined with its cost-effective and scalable production, positions it as a potentially transformative treatment for IBD, offering new avenues for personalized medical interventions.
研究领域:
药学
·
纳米技术
·
胃肠病学
·
免疫学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Cong Zhang,Qingrong Li,Jie Shan,Jianghao Xing,Xiaoyan Liu,Yan Ma,Haisheng Qian,Xulin Chen,Xianwen Wang,Lian-Ming Wu,Yue Yu
The overexpression of reactive oxygen and nitrogen species (RONS) in the colonic mucosa destroys the mucosa and its barrier, accelerating the occurrence of inflammatory bowel disease (IBD). The elimination of RONS from the inflammatory colon has proven effective in alleviating IBD. Although many nanoantioxidants have been developed, preparing robust and efficient nano-antioxidants remains challenging. Herein, by modifying bismuth selenide (Bi 2 Se 3 ) nanodiscs with polyvinylpyrrolidone (PVP), a multifunctional nanozyme based on 2D nanomaterials was developed for the treatment of IBD. By eliminating multiple RONS, such as hydroxyl radicals ( OH), superoxide anions (O 2 − ), nitric oxide (NO), and Bi 2 Se 3 nanodiscs enhanced cellular survival after H 2 O 2 stimulation. As evidenced by colonic injury, reduced body weight, spleen index, and proinflammatory cytokine levels in mice, RONS clearance alleviated intestinal inflammation in a prevention and delay model of acute colitis. 16S rDNA amplicon sequencing reveals that Bi 2 Se 3 nanodiscs had the potential to regulate intestinal flora , increase the proportion of Firmicutes to Bacteroidetes , inhibit Proteobacteria bacteria, and restore intestinal homeostasis . This study highlights the use of Bi 2 Se 3 nanodiscs with excellent biocompatibility, multienzyme functionality, and RONS scavenging ability as treatments for IBD without apparent adverse effects. Statement of Significance RONS were efficiently scavenged by Bi 2 Se 3 nanodiscs. Bi 2 Se 3 nanodiscs could be as a promising and potentially safe theraeputic agent for IBD. The gut microbiota could be modulated by Bi 2 Se 3 nanodiscs.
研究领域:
纳米技术
·
医学
·
胃肠病学
·
免疫学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Zeyuan Jin,Yaqi Zhang,Haijun Hu,Qian Li,Liwen Zhang,Kefei Zhao,Wenxing Liu,Lanjuan Li,Changyou Gao
Inflammatory bowel disease (IBD) is characterized by the upregulation of reactive oxygen species (ROS) and dysfunction of gut immune system, and microbiota. The conventional treatments mainly focus on symptom control with medication by overuse of drugs. There is an urgent need to develop a closed-loop strategy that combines in situ monitoring and precise treatment. Herein, we innovatively designed the ‘cluster munition structure’ theranostic microgels to realize the monitoring and therapy for ulcerative colitis (a subtype of IBD). The superoxide anion specific probe (tetraphenylethylene-coelenterazine, TPC) and ROS-responsive nanogels consisting of postbiotics urolithin A (UA) were loaded into alginate and ion-crosslinked to obtain the theranostic microgels. The theranostic microgels could be delivered to the inflammatory site, where the environment-triggered breakup of the microgels and release of the nanogels were achieved in sequence. The TPC-UA group had optimal results in reducing inflammation, repairing colonic epithelial tissue, and remodeling microbiota, leading to inflammation amelioration and recovery of tight junction between the colonic epithelium, and maintenance of gut microbiota. During the recovery process, the local chemiluminescence intensity, which is proportional to the degree of inflammation, was gradually inhibited. The cluster munition of theranostic microgels displayed promising outcomes in monitoring inflammation and precise therapy, and demonstrated the potential for inflammatory disease management.
研究领域:
药理学
·
生物医学工程
·
胃肠病学
·
免疫学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2024
·
IF 4.5
Hongming Tang,Tao Hou,Han Zhou,Han Liao,Fangfang Xu,Xiaomin Xie,Wenjie Yuan,Zhixin Guo,Yanfang Liu,Jixia Wang,Weijia Zhou,Xinmiao Liang
Histamine 4 receptor (H4R), the most recently identified subtype of histamine receptor, primarily induces inflammatory reactions upon activation. Several H4R antagonists have been developed for the treatment of inflammatory bowel disease (IBD) and atopic dermatitis (AD), but their use has been limited by adverse side effects, such as a short half-life and toxicity. Natural products, as an important source of anti-inflammatory agents, offer minimal side effects and reduced toxicity. This work aimed to identify novel H4R antagonists from natural products. An H4R target-pathway model deconvoluted downstream G i and MAPK signaling pathways was established utilizing cellular label-free integrative pharmacology (CLIP), on which 148 natural products were screened. Cryptotanshinone was identified as selective H4R antagonist, with an IC 50 value of 11.68 ± 1.30 μM, which was verified with Fluorescence Imaging Plate Reader (FLIPR) and Cellular Thermal Shift (CTS) assays. The kinetic binding profile revealed the noncompetitive antagonistic property of cryptotanshinone. Two allosteric binding sites of H4R were predicted using SiteMap, Fpocket and CavityPlus. Subsequent molecular docking and dynamics simulation indicated that cryptotanshinone interacts with H4R at a pocket formed by the outward interfaces between TM3/4/5, potentially representing a new allosteric binding site for H4R. Overall, this study introduced cryptotanshinone as a novel H4R antagonist, offering promise as a new hit for drug design of H4R antagonist. Additionally, this study provided a novel screening model for the discovery of H4R antagonists.
研究领域:
药理学
·
药物发现
·
炎症
·
天然产物化学
·
分子生物学
·
细胞信号传导
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Xu Zhang,Huan Yang,Ye He,Dan Zhang,Guifang Lu,Mudan Ren,Yi Lyu,Zhang Yuan,Shuixiang He
Excessive oxidative stress, dysregulated immune homeostasis, and disruption of the intestinal epithelial barrier are crucial features of inflammatory bowel disease (IBD). Traditional treatments focusing solely on inflammation resolution remain unsatisfactory. Herein, a yeast-inspired orally administered nanocomposite was developed. First, the MD@MPDA core was fabricated by integrating manganese dioxide (MnO2) nanozymes onto diallyl trisulfide (H2S prodrug)-loaded mesoporous polydopamine nanoparticles (MPDA). Then, yeast cell wall (YCW) was chosen to encapsulate MD@MPDA, namely, YMD@MPDA. The β-glucan embedded in the YCW shell not only protected the nanocomposite from the harsh gastrointestinal environment but also allowed the targeting enrichment in the inflamed colon. Furthermore, M1 macrophages triggered the intracellular GSH-responsive H2S release in the pathological microenvironment. MD@MPDA effectively alleviated inflammatory responses by MnO2-mediated ROS-scavenging and H2S-participated immunomodulation. The synergistic action contributed to macrophage mitochondrial function restoration and M2 polarization by suppressing NOX4 signaling and p38 MAPK pro-inflammatory signaling. In the mice model of dextran sulfate sodium (DSS)-induced IBD, the multipronged manner of scavenging oxidative stress, remodeling innate and adaptive immune homeostasis, and reshaping gut microbiota caused by YMD@MPDA effectively ameliorated inflammation and restored intestinal barrier functions. Overall, the YMD@MPDA nanocomposite provides a promising codelivery strategy of antioxidative nanozymes and gas prodrugs for the comprehensive management of IBD.
研究领域:
纳米医学
·
胃肠病学
·
免疫学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Shanshan Tie,Wentao Su,Yannan Chen,Shida Wu,Hao Wu,Yukun Song,Siyuan Fei,Mingqian Tan
The purpose of this study is to design a cell membrane and mitochondrial targeting nanoparticle with glutathione stimulus response to deliver procyanidin for effective treatment of inflammatory bowel disease (IBD). The dual targeting procyanidin nanoparticles were prepared with amphiphilic stearic acid modified hyaluronic acid using cystamine dihydrochloride as a linker for encapsulation of (5-carboxypentyl) (triphenyl) phosphonium bromide conjugated procyanidins. As expected, the procyanidin nanoparticles showed good mitochondrial targeting ability, with a Pearson’s correlation coefficient of 0.91 at 4 h. In vivo imaging of IBD mice model demonstrated a remarkable colon accumulation of the targeting procyanidin nanoparticles. Significant glutathione stimulus release of procyanidin was found in the presence of 10 mM of glutathione at pH 7.4. In vivo experiments showed that the colon length of targeting procyanidin nanoparticle-treated IBD mice increased by 20.84% compared with the IBD mice. The weight loss, disease activity index score, oxidative stress level and the release of proinflammatory cytokines were significantly ameliorated. The composition and relative abundance of gut microbiota, and the number of short chain fatty acids were improved upon the uptake of targeting procyanidin nanoparticles. This study provided a dual targeting and glutathione response strategy to improve the bioavailability of procyanidin in IBD treatment.
研究领域:
纳米技术
·
药学
·
炎症
·
胃肠病学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）