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Research Article | Open Access

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

Yajun Song1,† , Yang Li1,2,†, Wengang Hu1,3,†, Feng Li4, Hao Sheng1, Chibing Huang1, Xin Gou2, Jingming Hou5( ), Ji Zheng1( ), Ya Xiao1( )
Department of Urology, Xinqiao Hospital, The Army Medical University, No. 184, Xinqiao Street, Shapingba District, Chongqing, 400037, China
Department of Urology, The First Affiliated Hospital of Chongqing Medical University, No. 1, Yuanjiagang Road, Yuzhong District, Chongqing, 400016, China
Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burn and Combined Injury, Chongqing Key Laboratory for Disease Proteomics, Army Military Medical University, No. 30, Gaotanyan Street, Shapingba District, Chongqing, 400038, China
Department of Urology, Chongqing University Three Gorges Hospital, No. 165, Xincheng Road, Wanzhou District, Chongqing, 404031, China
Department of Rehabilitation, Southwest Hospital, The Army Medical University, No. 30, Gaotanyan Street, Shapingba District, Chongqing, 400038, China

†Yajun Song, Yang Li and Wengang Hu contributed equally to this work.

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Highlights

• The breakdown of intestinal barrier integrity occurs after severe burn injury and is responsible for the reactions of inflammation and oxidative stress.

• A new anti-inflammatory and antioxidant nanoparticle named LCD was developed, and its protective effects of severe burninduced intestinal injury were evaluated.

• LCD nanoparticles relieved the symptoms of burn-induced intestinal injury in a mouse model, and maintained the intestinal mechanical barrier through alleviating pro-inflammation factors (tumor necrosis factor-α, IL-17A) and ROS accumulation.

• LCD nanoparticles suppressed the increase in IL-17A and the proportion of IL-17A+Vγ4+ γδ T subtype cells that are considered important triggers in the early stage of inflammation.

Abstract

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 β-cyclodextrin (β-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-α, 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+Vγ4+ γδ T subtype cells was also observed in vitro in LPS-treated Vγ4+ γδ 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.

Graphical Abstract

References

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Burns & Trauma
Article number: tkad054

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Cite this article:
Song Y, Li Y, Hu W, et al. Luminol-conjugated cyclodextrin biological nanoparticles for the treatment of severe burn-induced intestinal barrier disruption. Burns & Trauma, 2024, 12: tkad054. https://doi.org/10.1093/burnst/tkad054

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Received: 19 March 2023
Revised: 14 October 2023
Accepted: 14 October 2023
Published: 10 October 2026
© The Author(s) 2024. Published by Oxford University Press.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permitsunrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.