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

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 recognit...

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Main Authors: Yue Li, Hu Li, Zhiwei Hu, Yayue Zhang, Xuran Ding, Xinjie Huang, Yabing Hua, Lin Sun, Ye Li, Ziming Zhao, Yuan He
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Journal of Lipid Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S0022227525000598
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author Yue Li
Hu Li
Zhiwei Hu
Yayue Zhang
Xuran Ding
Xinjie Huang
Yabing Hua
Lin Sun
Ye Li
Ziming Zhao
Yuan He
author_facet Yue Li
Hu Li
Zhiwei Hu
Yayue Zhang
Xuran Ding
Xinjie Huang
Yabing Hua
Lin Sun
Ye Li
Ziming Zhao
Yuan He
author_sort Yue Li
collection DOAJ
description 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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issn 0022-2275
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publishDate 2025-05-01
publisher Elsevier
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series Journal of Lipid Research
spelling doaj-art-e4649ab542024933bdcc486a9e945d772025-08-20T02:14:24ZengElsevierJournal of Lipid Research0022-22752025-05-0166510079910.1016/j.jlr.2025.100799Phosphatidylserine-decorated delivery platform helps alleviate acute lung injury via potentiating macrophage targetingYue Li0Hu Li1Zhiwei Hu2Yayue Zhang3Xuran Ding4Xinjie Huang5Yabing Hua6Lin Sun7Ye Li8Ziming Zhao9Yuan He10School of Medical Technology, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaSchool of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaThe Second Clinical Medical School, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaSchool of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaSchool of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaSchool of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaSchool of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaDepartment of Zhuhai Campus of Zunyi Medical University, Zhuhai, ChinaThe Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, ChinaSchool of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, China; For correspondence: Ziming Zhao; Yuan HeSchool of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, China; For correspondence: Ziming Zhao; Yuan HeAcute 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.http://www.sciencedirect.com/science/article/pii/S0022227525000598phosphatidylserinedecorationmacrophagedelivery platformacute lung injuryapoptotic cell
spellingShingle Yue Li
Hu Li
Zhiwei Hu
Yayue Zhang
Xuran Ding
Xinjie Huang
Yabing Hua
Lin Sun
Ye Li
Ziming Zhao
Yuan He
Phosphatidylserine-decorated delivery platform helps alleviate acute lung injury via potentiating macrophage targeting
Journal of Lipid Research
phosphatidylserine
decoration
macrophage
delivery platform
acute lung injury
apoptotic cell
title Phosphatidylserine-decorated delivery platform helps alleviate acute lung injury via potentiating macrophage targeting
title_full Phosphatidylserine-decorated delivery platform helps alleviate acute lung injury via potentiating macrophage targeting
title_fullStr Phosphatidylserine-decorated delivery platform helps alleviate acute lung injury via potentiating macrophage targeting
title_full_unstemmed Phosphatidylserine-decorated delivery platform helps alleviate acute lung injury via potentiating macrophage targeting
title_short Phosphatidylserine-decorated delivery platform helps alleviate acute lung injury via potentiating macrophage targeting
title_sort phosphatidylserine decorated delivery platform helps alleviate acute lung injury via potentiating macrophage targeting
topic phosphatidylserine
decoration
macrophage
delivery platform
acute lung injury
apoptotic cell
url http://www.sciencedirect.com/science/article/pii/S0022227525000598
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