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磷脂酰丝氨酸修饰的递送平台通过增强巨噬细胞靶向作用有助于减轻急性肺损伤。

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

作者信息

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

机构信息

School of Medical Technology, Xuzhou Medical University, Xuzhou, Jiangsu, China.

School of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, China.

出版信息

J Lipid Res. 2025 May;66(5):100799. doi: 10.1016/j.jlr.2025.100799. Epub 2025 Apr 10.

DOI:10.1016/j.jlr.2025.100799
PMID:40216334
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12127575/
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.

摘要

急性肺损伤（ALI）是一种具有高发病率和死亡率的危及生命的炎症性疾病。开发更有效的ALI治疗策略迫在眉睫。凋亡细胞表面表达的磷脂酰丝氨酸（PtdSer）不仅能促进巨噬细胞的结合与识别，还能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外表面修饰合成的PtdSer设计了一种模拟凋亡细胞的纳米颗粒。结果表明，与未修饰的聚乳酸-乙醇酸纳米颗粒相比，修饰PtdSer的聚乳酸-乙醇酸纳米颗粒（PSNPs）具有抗炎特性并增强了巨噬细胞吞噬作用。载有地塞米松的PSNPs在体外对巨噬细胞表现出卓越的抗炎活性。体内研究还表明，修饰PtdSer可增加肺部给药后纳米颗粒在肺巨噬细胞中的蓄积。载有地塞米松的PSNPs在肺巨噬细胞中的蓄积有效减轻了炎症肺组织中的炎症，并进一步缓解了ALI综合征。总之，修饰PtdSer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递送平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0e/12127575/f7fd669b19af/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0e/12127575/bbb9eca9ddb1/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0e/12127575/14f199dd2ca4/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0e/12127575/85ac7b35acd4/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0e/12127575/28635108fc71/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0e/12127575/cf2482909d91/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0e/12127575/9c04bb92451b/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0e/12127575/332eb62c8d85/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0e/12127575/f7fd669b19af/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0e/12127575/bbb9eca9ddb1/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0e/12127575/14f199dd2ca4/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0e/12127575/85ac7b35acd4/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0e/12127575/28635108fc71/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0e/12127575/cf2482909d91/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0e/12127575/9c04bb92451b/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0e/12127575/332eb62c8d85/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0e/12127575/f7fd669b19af/gr8.jpg

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