Citation: Yikun Chen, Wenling Li, Juan Cao, Yongjun Wang, Yufang Guo, Liu Qing, Li Wang, Sisi Yu, Lei Xing, Hulin Jiang, Bing Wan. Break the vicious cycle and remodel the malignant inflammatory microenvironment in ARDS with efferocytosis-informed nanodrugs[J]. Chinese Chemical Letters, ;2026, 37(7): 111722. doi: 10.1016/j.cclet.2025.111722 shu

Break the vicious cycle and remodel the malignant inflammatory microenvironment in ARDS with efferocytosis-informed nanodrugs

Yikun Chen ^{a, 1} ,
Wenling Li ^{b, 1} ,
Juan Cao ^{b, 1} ,
Yongjun Wang ^c ,
Yufang Guo ^c ,
Liu Qing ^a ,
Li Wang ^c ,
Sisi Yu ^b ,
Lei Xing ^{b, *,} ,
Hulin Jiang ^{b, *,} ,
Bing Wan ^{c, *,}

a.
Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, China
b.
State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China
c.
Department of Respiratory and Critical Care Medicine, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing 210000, China

xinglei6xl@163.com

jianghulin3@163.com

bingwan76@163.com

Received Date: 10 April 2025
Revised Date: 13 August 2025
Accepted Date: 14 August 2025
Available Online: 15 August 2025

Figures(5)

Acute respiratory distress syndrome (ARDS) is one of the diseases with a significant mortality rate due to respiratory failure. Yet, malignant microenvironment (MM) composed mainly of inflammatory cytokines (IC) and reactive oxygen species (ROS) limit the therapeutic effect. Herein we construct the nanoparticles (NPs) BSA-MnO₂@Tan-IIA/PSLs (BMTPLs) to disrupt the vicious cycle between IC and ROS by suppressing IC production and scavenging ROS, which effectively remodels the MM of ARDS. The BMTPLs composed of the water-dispersible BSA-MnO₂ (BM) and phosphatidylserine (PS)-consisting lipid shell containing lipophilic tanshinone IIA (Tan-IIA). After phagocytosed by activated macrophages (M1) in an efferocytosis-like manner originating from the PS effect, the released Tan-IIA inhibit NF-κB pathway and further suppresses the secretion of IC. Concurrently, BM scavenging ROS alleviates the oxidative stress microenvironment, which deeply enhances the anti-inflammation effect of Tan-IIA. Moreover, the low-level ROS and down-regulation IC promote the transformation from pro-inflammatory M1 to anti-inflammatory M2 contributing to restoring tissue homeostasis. The results in vitro and in vivo indicate that the MM of ARDS can be effectively remodeled by BMTPLs, which holds great potential for ARDS treatment.
- ARDS,
- Vicious cycle,
- Malignant microenvironment,
- Inflammation,
- Efferocytosis,
- Tan-IIA
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