Development of activated endothelial targeted high-density lipoprotein nanoparticles

Minzhi Yu; Kristen Hong; Reheman Adili; Ling Mei; Lisha Liu; Lisha Liu; Hongliang He; Hongliang He; Yanhong Guo; Y. Eugene Chen; Michael Holinstat; Michael Holinstat; Anna Schwendeman

doi:10.3389/fphar.2022.902269

Frontiers in Pharmacology (Aug 2022)

Development of activated endothelial targeted high-density lipoprotein nanoparticles

Minzhi Yu,
Kristen Hong,
Reheman Adili,
Ling Mei,
Lisha Liu,
Lisha Liu,
Hongliang He,
Hongliang He,
Yanhong Guo,
Y. Eugene Chen,
Michael Holinstat,
Michael Holinstat,
Anna Schwendeman

Affiliations

Minzhi Yu: Department of Pharmaceutical Sciences and the Biointerfaces Institute, University of Michigan, Ann Arbor, MI, United States
Kristen Hong: Department of Pharmaceutical Sciences and the Biointerfaces Institute, University of Michigan, Ann Arbor, MI, United States
Reheman Adili: Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, United States
Ling Mei: Department of Pharmaceutical Sciences and the Biointerfaces Institute, University of Michigan, Ann Arbor, MI, United States
Lisha Liu: Department of Pharmaceutical Sciences and the Biointerfaces Institute, University of Michigan, Ann Arbor, MI, United States
Lisha Liu: Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, China
Hongliang He: Department of Pharmaceutical Sciences and the Biointerfaces Institute, University of Michigan, Ann Arbor, MI, United States
Hongliang He: State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China
Yanhong Guo: Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI, United States
Y. Eugene Chen: Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI, United States
Michael Holinstat: Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, United States
Michael Holinstat: Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI, United States
Anna Schwendeman: Department of Pharmaceutical Sciences and the Biointerfaces Institute, University of Michigan, Ann Arbor, MI, United States

DOI: https://doi.org/10.3389/fphar.2022.902269
Journal volume & issue: Vol. 13

Abstract

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Endothelial inflammation is an important pathophysiological driving force in various acute and chronic inflammatory diseases. High-density lipoproteins (HDLs) play critical roles in regulating endothelial functions and resolving endothelial inflammation. In the present study, we developed synthetic HDLs (sHDLs) which actively target inflamed endothelium through conjugating vascular cell adhesion protein 1 (VCAM-1) specific VHPK peptide. The active targeting of VHPK-sHDLs was confirmed in vitro on TNF-α activated endothelial cells. VHPK-sHDLs presented potent anti-inflammatory efficacies in vitro through the reduction of proinflammatory cytokine production and inhibition of leukocyte adhesion to activated endothelium. VHPK-sHDLs showed increased binding on inflamed vessels and alleviated LPS-induced lung inflammation in vivo. The activated endothelium-targeted sHDLs may be further optimized to resolve endothelial inflammation in various inflammatory diseases.

Published in Frontiers in Pharmacology

ISSN: 1663-9812 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://journal.frontiersin.org/journals/pharmacology

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