ROS Scavenging and inflammation-directed polydopamine nanoparticles regulate gut immunity and flora therapy in inflammatory bowel disease

被引:59
作者
Bao, Meiyu [1 ]
Wang, Keyi [2 ]
Li, Jingqiang [1 ]
Li, Yueying [3 ]
Zhu, Huanhuan [1 ]
Lu, Meiling [1 ]
Zhang, Yue [1 ]
Fan, Qiangyuan [1 ]
Han, Lin [1 ]
Wang, Kesheng [1 ]
Wang, Dongyan [4 ]
Gao, Yan [1 ]
Peng, Bo [2 ]
Ming, Zunzhen [1 ]
Liu, Weiwei [5 ]
机构
[1] Tongji Univ, Shanghai Tenth Peoples Hosp, Sch Med, Cent Lab, 301 Yanchang Middle Rd, Shanghai 200072, Peoples R China
[2] Tongji Univ, Shanghai Tenth Peoples Hosp, Dept Urol, Sch Med, Shanghai 200060, Peoples R China
[3] Tongji Univ, Shanghai Tenth Peoples Hosp, Sch Med, Dept Lab Med, Shanghai 200070, Peoples R China
[4] Shanghai Pudong New Area Gongli Hosp, Dept Gastroenterol, Shanghai 200135, Peoples R China
[5] Shanghai Univ Tradit Chinese Med, Longhua Hosp, Dept Lab Med, 725 South Wanping Rd, Shanghai 200032, Peoples R China
基金
中国国家自然科学基金;
关键词
Polydopamine nanoparticles; Antimicrobial peptides; Immunoregulation; Intestinal microbe; Inflammatory Bowel Disease; BARRIER FUNCTION; MICROBIOTA; CATHELICIDIN; IBD;
D O I
10.1016/j.actbio.2023.02.026
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Dysfunction of the intestinal mucosal immune system and dysbiosis of the intestinal microflora can in-duce inflammatory bowel disease. However, drug-mediated clinical treatment remains a challenge due to its poor therapeutic efficacy and severe side effects. Herein, a ROS scavenging and inflammation-directed nanomedicine is designed and fabricated by coupling polydopamine nanoparticles with mCRAMP, an antimicrobial peptide, while wrapping macrophage membrane in the outer layer. The designed nanomedicine reduced the secretion of pro-inflammatory cytokines and elevate the expression of anti-inflammatory cytokine in vivo and in vitro inflammation models, demonstrating its significant ability of improving inflammatory responses. Importantly, the macrophage membrane encapsulated nanoparticles exhibit the obviously enhanced targeting performance in local inflamed tissues. Furthermore, the 16S rRNA sequencing of fecal microorganisms showed that probiotics increased and pathogenic bacteria were inhibited after oral delivery the nanomedicine, indicating that the designed nano platform played a signif-icant role in optimizing intestinal microbiome. Taken together, the designed nanomedicine are not only easy to prepare and exhibit high biocompatibility, but also show the inflammatory targeting property, anti-inflammatory function and positive regulation of intestinal flora, thus providing a new idea for the intervention and treatment of colitis. Statement of significance Inflammatory bowel disease (IBD), a chronic and intractable disease, may lead to colon cancer in severe cases without effective treatment. However, clinical drugs are largely ineffective owing to insufficient therapeutic efficacies and side effects. Herein, we constructed a biomimetic polydopamine nanoparti-cle for oral administration to treat the IBD by modulating mucosal immune homeostasis and optimiz-ing intestinal microorganisms. In vitro and in vivo experiments showed that the designed nanomedicine not only exhibits the anti-inflammatory function and inflammatory targeting property but also positively regulate the gut microflora. Taken together, the designed nanomedicine combined immunoregulation and intestinal microecology modulation to significantly enhance the therapeutic effect on colitis in mice, thus providing a new approach for the clinical treatment of colitis.(c) 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:250 / 264
页数:15
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