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生物相容的 N-乙酰化纳米构建体减轻体内脂多糖诱导的急性肺损伤。

Biocompatible N-acetyl-nanoconstruct alleviates lipopolysaccharide-induced acute lung injury in vivo.

机构信息

Biomaterials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, 93 Jungbu-daero, Paldal-gu, Suwon, Republic of Korea.

出版信息

Sci Rep. 2021 Nov 22;11(1):22662. doi: 10.1038/s41598-021-01624-5.

DOI:10.1038/s41598-021-01624-5
PMID:34811378
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8608841/
Abstract

Oxidative stress plays important roles in inflammatory responses during acute lung injury (ALI). Recently, nanoconstruct (Nano)-based drug-delivery systems have shown promise in many models of inflammation. In this study, we evaluated the anti-inflammatory effects of N-acetylcysteine (NAC) loaded in a biocompatible Nano using a rat model of ALI. We synthesized a Nano with a good NAC-releasing capacity using porous silica Nano, which was used to produce Nano/NAC complexes. For in vivo experiments, Sprague-Dawley rats were intraperitoneally administered NAC or Nano/NAC 30 min after intratracheal instillation of lipopolysaccharide. After 6 h, bronchoalveolar lavage fluids and lung tissues were collected. The anti-oxidative effect of the Nano/NAC complex was confirmed by demonstrating reduced levels of reactive oxygen species after treatment with the Nano/NAC in vitro. In vivo experiments also showed that the Nano/NAC treatment may protect against LPS-induced ALI thorough anti-oxidative and anti-inflammatory effects, which may be attributed to the inactivation of the NF-κB and MAPK pathways. In addition, the effects of Nano/NAC treatment were shown to be superior to those of NAC alone. We suggest the therapeutic potential of Nano/NAC treatment as an anti-inflammatory agent against ALI. Furthermore, our study can provide basic data for developing nanotechnology-based pharmacotherapeutics for ALI.

摘要

氧化应激在急性肺损伤 (ALI) 的炎症反应中发挥重要作用。最近,基于纳米结构(Nano)的药物输送系统在许多炎症模型中显示出了潜力。在这项研究中,我们使用 ALI 大鼠模型评估了负载在生物相容性 Nano 中的 N-乙酰半胱氨酸 (NAC) 的抗炎作用。我们使用多孔硅 Nano 合成了一种具有良好 NAC 释放能力的 Nano,用于制备 Nano/NAC 复合物。对于体内实验,Sprague-Dawley 大鼠在气管内滴注脂多糖后 30 分钟经腹腔给予 NAC 或 Nano/NAC。6 小时后,收集支气管肺泡灌洗液和肺组织。通过证明 Nano/NAC 复合物在体外处理后活性氧水平降低,证实了 Nano/NAC 复合物的抗氧化作用。体内实验还表明,Nano/NAC 治疗可能通过抗氧化和抗炎作用来预防 LPS 诱导的 ALI,这可能归因于 NF-κB 和 MAPK 途径的失活。此外,Nano/NAC 治疗的效果优于 NAC 单独治疗。我们建议将 Nano/NAC 治疗作为一种针对 ALI 的抗炎药物的治疗潜力。此外,我们的研究可以为开发基于纳米技术的 ALI 治疗药物提供基础数据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/974b/8608841/18fe70e8953b/41598_2021_1624_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/974b/8608841/aa55c44bea54/41598_2021_1624_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/974b/8608841/84e9845502d1/41598_2021_1624_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/974b/8608841/4d129b76a541/41598_2021_1624_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/974b/8608841/d43ad4ff6c0a/41598_2021_1624_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/974b/8608841/d861cc31526e/41598_2021_1624_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/974b/8608841/18fe70e8953b/41598_2021_1624_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/974b/8608841/aa55c44bea54/41598_2021_1624_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/974b/8608841/b8075887d7e9/41598_2021_1624_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/974b/8608841/c3b666f04ece/41598_2021_1624_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/974b/8608841/84e9845502d1/41598_2021_1624_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/974b/8608841/4d129b76a541/41598_2021_1624_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/974b/8608841/d43ad4ff6c0a/41598_2021_1624_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/974b/8608841/d861cc31526e/41598_2021_1624_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/974b/8608841/18fe70e8953b/41598_2021_1624_Fig8_HTML.jpg

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