Development of activated endothelial targeted high-density lipoprotein nanoparticles

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

doi:10.3389/fphar.2022.902269

Development of activated endothelial targeted high-density lipoprotein nanoparticles

Front Pharmacol. 2022 Aug 29:13:902269. doi: 10.3389/fphar.2022.902269. eCollection 2022.

Authors

Minzhi Yu¹, Kristen Hong¹, Reheman Adili², Ling Mei¹, Lisha Liu^{1

3}, Hongliang He^{1

4}, Yanhong Guo⁵, Y Eugene Chen⁵, Michael Holinstat^{2

5}, Anna Schwendeman¹

Affiliations

¹ Department of Pharmaceutical Sciences and the Biointerfaces Institute, University of Michigan, Ann Arbor, MI, United States.
² Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, United States.
³ Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, China.
⁴ State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.
⁵ Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI, United States.

Abstract

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.

Keywords: VCAM-1; anti-inflammation; endothelium; high-density lipoprotein; inflammation.

Abstract

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