Luminol-conjugated cyclodextrin biological nanoparticles for the treatment of severe burn-induced intestinal barrier disruption

作者全名："Song, Yajun; Li, Yang; Hu, Wengang; Li, Feng; Sheng, Hao; Huang, Chibing; Gou, Xin; Hou, Jingming; Zheng, Ji; Xiao, Ya"

作者地址："[Song, Yajun; Li, Yang; Hu, Wengang; Sheng, Hao; Huang, Chibing; Zheng, Ji; Xiao, Ya] Army Med Univ, Affiliated Hosp 2, Dept Urol, 184 Xinqiao St, Chongqing 400037, Peoples R China; [Li, Yang; Gou, Xin] Chongqing Med Univ, Dept Urol, Affiliated Hosp 1, 1,Yuanjiagang Rd, Chongqing 400016, Peoples R China; [Hu, Wengang] Army Mil Med Univ, Southwest Hosp, Inst Burn Res, State Key Lab Trauma Burn & Combined Injury,Chongq, 30,Gaotanyan St, Chongqing 400038, Peoples R China; [Li, Feng] Chongqing Univ Three Gorges Hosp, Dept Urol, 165,Xincheng Rd, Chongqing 404031, Peoples R China; [Hou, Jingming] Army Med Univ, Southwest Hosp, Dept Rehabil, 30,Gaotanyan St, Chongqing 400038, Peoples R China"

通信作者："Zheng, J; Xiao, Y (通讯作者)，Army Med Univ, Affiliated Hosp 2, Dept Urol, 184 Xinqiao St, Chongqing 400037, Peoples R China.; Hou, JM (通讯作者)，Army Med Univ, Southwest Hosp, Dept Rehabil, 30,Gaotanyan St, Chongqing 400038, Peoples R China."

来源：BURNS & TRAUMA

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001180109300001

JCR分区：Q1

影响因子：5.3

年份：2024

卷号：12

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：LCD nanoparticle; Burn; Intestinal barrier; Inflammatory cytokines; reactive oxygen species; V gamma 4+gamma delta T cells; Luminol-conjugated cyclodextrin

摘要："Background: The breakdown of intestinal barrier integrity occurs after severe burn injury and is responsible for the subsequent reactions of inflammation and oxidative stress. A new protective strategy for the intestinal barrier is urgently needed due to the limitations of the traditional methods. Recently, the application of nanoparticles has become one of the promising therapies for many inflammation-related diseases or oxidative damage. Herein, we developed a new anti-inflammatory and antioxidant nanoparticle named luminol-conjugated cyclodextrin (LCD) and aimed to evaluate its protective effects in severe burn-induced intestinal injury. Methods: First, LCD nanoparticles, engineered with covalent conjugation between luminol and beta-cyclodextrin (beta-CD), were synthesized and examined. Then a mouse burn model was successfully established before the mouse body weight, intestinal histopathological manifestation, permeability, tight junction (TJ) expression and pro-inflammatory cytokines were determined in different groups. The proliferation, apoptosis, migration and reactive oxygen species (ROS) of intestinal epithelial cells (IECs) were assessed. Intraepithelial lymphocytes (IELs) were isolated and cultured for analysis by flow cytometry. Results: LCD nanoparticle treatment significantly relieved the symptoms of burn-induced intestinal injury in the mouse model, including body weight loss and intestinal permeability abnormalities. Moreover, LCD nanoparticles remarkably recovered the mechanical barrier of the intestine after severe burn, renewed TJ structures, promoted IEC proliferation and migration, and inhibited IEC apoptosis. Mechanistically, LCD nanoparticles dramatically alleviated pro-inflammation factors (tumor necrosis factor-alpha, IL-17A) and ROS accumulation, which could be highly involved in intestinal barrier disruption. Furthermore, an increase in IL-17A and the proportion of IL-17A+V gamma 4+ gamma delta T subtype cells was also observed in vitro in LPS-treated V gamma 4+ gamma delta T cells, but the use of LCD nanoparticles suppressed this increase. Conclusions: Taken together, these findings demonstrate that LCD nanoparticles have the protective ability to ameliorate intestinal barrier disruption and provide a therapeutic intervention for burn-induced intestinal injury. [GRAPHICS]"

基金机构：General Project of Natural Science Foundation Project of Chongqing [cstc2021jcyj-msxmX0611]; Chongqing Doctor "Through Train" Scientific Research Project [CSTBBSXM2022-JCX0007]; Education and Training Reform Project of the Army Medical University [CSTBBSXM2022-JCX0007]

基金资助正文："This work was supported by the General Project of Natural Science Foundation Project of Chongqing (No. cstc2021jcyj-msxmX0611), the Chongqing Doctor ""Through Train"" Scientific Research Project (CSTBBSXM2022-JCX0007), and the Education and Training Reform Project of the Army Medical University (CSTBBSXM2022-JCX0007)."