Phosphatidylserine-decorated delivery platform helps alleviate acute lung injury via potentiating macrophage targeting.

IF 5 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Lipid Research Pub Date : 2025-04-10 DOI:10.1016/j.jlr.2025.100799

Yue Li, Hu Li, Zhiwei Hu, Yayue Zhang, Xuran Ding, Xinjie Huang, Yabing Hua, Lin Sun, Ye Li, Ziming Zhao, Yuan He

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引用次数: 0

Abstract

Acute lung injury (ALI) is a life-threatening inflammatory disease with high morbidity and mortality. It is urgent to develop more effective therapeutic strategies against ALI. Phosphatidylserine (PtdSer) expressed on the surface of apoptotic cells not only allows for macrophage binding and recognition but also drives anti-inflammatory signaling within the macrophage. In this study, we designed an apoptotic cell-mimicry nanoparticle by decorating synthetic PtdSer on the outer face of nanoparticles. The results indicated that PtdSer-decorated poly(lactic-co-glycolic acid) nanoparticles (PSNPs) showed anti-inflammatory properties and increased macrophage phagocytosis in relative to the nondecorated poly(lactic-co-glycolic acid nanoparticles. Dexamethasone-loaded PSNPs exhibited superior anti-inflammatory activity on macrophages in vitro. In vivo studies also showed that PtdSer decoration increased the accumulation of nanoparticles in lung macrophages after pulmonary administration. Accumulation of dexamethasone-loaded PSNPs in lung macrophages effectively reduced inflammation in inflamed lungs and further alleviated ALI syndromes. In conclusion, PtdSer decoration not only endows the anti-inflammatory function to nanocarriers but also potentiates its macrophage targeting in the inflamed microenvironment, which offers an ideal drug delivery platform for ALI therapy.

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磷脂酰丝氨酸修饰的传递平台通过增强巨噬细胞靶向减轻急性肺损伤。

急性肺损伤（ALI）是一种危及生命的炎症性疾病，具有很高的发病率和死亡率。迫切需要开发更有效的治疗策略来对抗ALI。凋亡细胞表面表达的磷脂酰丝氨酸（PtdSer）不仅允许巨噬细胞结合和识别，还可以驱动巨噬细胞内的抗炎信号传导。在本研究中，我们通过在纳米颗粒的外表面修饰合成PtdSer，设计了一种模拟凋亡细胞的纳米颗粒。结果表明，ptdser修饰的聚乳酸-羟基乙酸纳米粒子（PSNPs）与未修饰的聚乳酸-羟基乙酸纳米粒子相比，具有抗炎和增强巨噬细胞吞噬的作用。负载地塞米松的psnp在体外对巨噬细胞表现出优异的抗炎活性。体内研究也表明，PtdSer修饰增加了肺给药后肺巨噬细胞中纳米颗粒的积累。负载地塞米松的psnp在肺巨噬细胞中的积累有效地减轻了炎症肺的炎症，并进一步缓解了ALI综合征。综上所述，PtdSer修饰不仅赋予纳米载体抗炎功能，还增强了其在炎症微环境中的巨噬细胞靶向性，为ALI治疗提供了理想的药物传递平台。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Lipid Research 生物-生化与分子生物学

CiteScore

11.10

自引率

4.60%

发文量

146

审稿时长

41 days

期刊介绍： The Journal of Lipid Research (JLR) publishes original articles and reviews in the broadly defined area of biological lipids. We encourage the submission of manuscripts relating to lipids, including those addressing problems in biochemistry, molecular biology, structural biology, cell biology, genetics, molecular medicine, clinical medicine and metabolism. Major criteria for acceptance of articles are new insights into mechanisms of lipid function and metabolism and/or genes regulating lipid metabolism along with sound primary experimental data. Interpretation of the data is the authors’ responsibility, and speculation should be labeled as such. Manuscripts that provide new ways of purifying, identifying and quantifying lipids are invited for the Methods section of the Journal. JLR encourages contributions from investigators in all countries, but articles must be submitted in clear and concise English.