Improving the circulation time and renal therapeutic potency of extracellular vesicles using an endogenous ligand binding strategy.

Abstract

Kidney diseases are a serious health issue worldwide, and novel therapeutics are urgently needed. Extracellular vesicles (EVs) have emerged as potent drug delivery systems (DDSs), but their therapeutic potential is limited by short circulation times and insufficient renal retention. Here, we report that endogenous ligand (albumin, ALB) binding is an efficient modification strategy to improve the therapeutic potency of EV-based DDSs for kidney diseases. Surface albumin-binding peptide (ABP)-displayed EVs (ABP-EVs) were produced by transfecting parent cells with the ABP-Lamp2b fusion plasmid. Compared with unmodified EVs (NC-EVs), ABP-EVs showed increased binding to ALB in vitro and elevated circulation time and multiple organ retention in vivo after systemic (iv) injection. Moreover, ABP-EVs had higher renal retention than NC-EVs in mice with acute kidney injury through a complex mechanism involving microvascular injury and megalin-mediated endocytosis. As a result, delivery of small molecule drugs (e.g., curcumin) or proteins (e.g., hepatocyte growth factor) by ABP-EVs had superior therapeutic (e.g., anti-apoptotic, antioxidant, anti-inflammatory) effects in vitro and in vivo. This study highlights that ABP-EVs are versatile DDSs for kidney diseases and provides insights into the new strategies of engineering EVs for drug delivery.

• Authors: Shuyun Liu, Ke Lv, Yizhuo Wang, Peng Lou, Pingya Zhou, Chengshi Wang, Lan Li, Guangneng Liao, Yong Zhang, Younan Chen, Jingqiu Cheng, Yanrong Lu, Jingping Liu
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 352 Pg. 1009-1023 (12 2022) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 36375619 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• Ligands
• Peptides
• Albumins

Topics

• Mice
• Animals
• Ligands
• Extracellular Vesicles (metabolism)
• Kidney
• Kidney Diseases (drug therapy, metabolism)
• Peptides (metabolism)
• Albumins (metabolism)