Macrophage-Associated Delivery of Tectorigenin by MOF818 Nanozyme for the Treatment of LPS-Induced Acute Lung Injury.
- 1School of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, Hubei, People's Republic of China.
Abstract
Introduction
Acute lung injury (ALI) is a life-threatening inflammatory pulmonary disorder characterized by excessive inflammation, oxidative stress, and disruption of lung tissue integrity. Macrophage dysregulation plays a critical role in the progression of ALI, making macrophage modulation a potential therapeutic strategy. Tectorigenin (Tec), a natural isoflavonoid with anti-inflammatory activity, has shown protective effects in inflammatory disorders, but its underlying mechanism and macrophage-targeted delivery in ALI remain unclear. Here, we developed a macrophage membrane-camouflaged MOF818 nanozyme for macrophage-targeted delivery of Tec, termed T-M@MM, to enhance its therapeutic efficacy against ALI.Methods
The effects of Tec and T-M@MM were evaluated in LPS-induced ALI mice and LPS- or TBHP-stimulated RAW264.7 macrophages. Macrophage depletion, network pharmacology, molecular docking, and cellular thermal shift assay were used to investigate the underlying mechanisms. Macrophage polarization, glycolysis, oxidative stress, mitochondrial function, and apoptosis were assessed using molecular and cellular assays. The physicochemical properties, Tec loading and release profiles, macrophage uptake, pulmonary biodistribution, biosafety, and therapeutic efficacy of T-M@MM were further evaluated.Results
Tec alleviated pulmonary inflammation and oxidative stress and promoted an anti-inflammatory macrophage phenotype, whereas macrophage depletion attenuated these effects. PFKFB3 was identified as a potential molecular target associated with the effects of Tec, and Tec suppressed PFKFB3-associated glycolysis and promoted anti-inflammatory macrophage polarization, which was attenuated by PFKFB3 overexpression. T-M@MM enabled Tec loading and exhibited pH/ROS-responsive release, enhanced macrophage uptake and pulmonary retention (>48 h), and potent ROS-scavenging activity. In LPS-induced ALI mice, T-M@MM alleviated pulmonary inflammation, oxidative stress, edema, and pathological injury without obvious abnormalities in major-organ histology, liver or kidney function, or body weight.Conclusion
T-M@MM integrates macrophage targeting, ROS scavenging, and Tec-mediated modulation of PFKFB3-associated glycolysis to regulate macrophage responses and ameliorate LPS-induced ALI, with preliminary evidence of favorable biocompatibility, providing a potential macrophage-targeted nanotherapeutic strategy.
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BibTeX
@article{wang2026macrophageassociated,
title = {{Macrophage-Associated Delivery of Tectorigenin by MOF818 Nanozyme for the Treatment of LPS-Induced Acute Lung Injury.}},
author = {Miao Wang and Shuhan Zhou and Ningfeng Mao and Yang Zhang and Chaoqun Huang and Bichao Lu},
journal = {International journal of nanomedicine},
year = {2026},
month = oct,
doi = {10.2147/ijn.s634246},
url = {https://europepmc.org/article/MED/42959962},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Macrophage-Associated Delivery of Tectorigenin by MOF818 Nanozyme for the Treatment of LPS-Induced Acute Lung Injury.
AU - Miao Wang
AU - Shuhan Zhou
AU - Ningfeng Mao
AU - Yang Zhang
AU - Chaoqun Huang
AU - Bichao Lu
PY - 2026
DA - 2026/10/25
JO - International journal of nanomedicine
DO - 10.2147/ijn.s634246
UR - https://europepmc.org/article/MED/42959962
AB - Introduction Acute lung injury (ALI) is a life-threatening inflammatory pulmonary disorder characterized by excessive inflammation, oxidative stress, and disruption of lung tissue integrity. Macrophage dysregulation plays a critical role in the progression of ALI, making macrophage modulation a potential therapeutic strategy. Tectorigenin (Tec), a natural isoflavonoid with anti-inflammatory activity, has shown protective effects in inflammatory disorders, but its underlying mechanism and macrophage-targeted delivery in ALI remain unclear. Here, we developed a macrophage membrane-camouflaged MOF818 nanozyme for macrophage-targeted delivery of Tec, termed T-M@MM, to enhance its therapeutic efficacy against ALI.Methods The effects of Tec and T-M@MM were evaluated in LPS-induced ALI mice and LPS- or TBHP-stimulated RAW264.7 macrophages. Macrophage depletion, network pharmacology, molecular docking, and cellular thermal shift assay were used to investigate the underlying mechanisms. Macrophage polarization, glycolysis, oxidative stress, mitochondrial function, and apoptosis were assessed using molecular and cellular assays. The physicochemical properties, Tec loading and release profiles, macrophage uptake, pulmonary biodistribution, biosafety, and therapeutic efficacy of T-M@MM were further evaluated.Results Tec alleviated pulmonary inflammation and oxidative stress and promoted an anti-inflammatory macrophage phenotype, whereas macrophage depletion attenuated these effects. PFKFB3 was identified as a potential molecular target associated with the effects of Tec, and Tec suppressed PFKFB3-associated glycolysis and promoted anti-inflammatory macrophage polarization, which was attenuated by PFKFB3 overexpression. T-M@MM enabled Tec loading and exhibited pH/ROS-responsive release, enhanced macrophage uptake and pulmonary retention (>48 h), and potent ROS-scavenging activity. In LPS-induced ALI mice, T-M@MM alleviated pulmonary inflammation, oxidative stress, edema, and pathological injury without obvious abnormalities in major-organ histology, liver or kidney function, or body weight.Conclusion T-M@MM integrates macrophage targeting, ROS scavenging, and Tec-mediated modulation of PFKFB3-associated glycolysis to regulate macrophage responses and ameliorate LPS-induced ALI, with preliminary evidence of favorable biocompatibility, providing a potential macrophage-targeted nanotherapeutic strategy.
SN - 1176-9114
SN - 1178-2013
ER -