PMID- 36375619 OWN - NLM STAT- MEDLINE DCOM- 20221206 LR - 20221212 IS - 1873-4995 (Electronic) IS - 0168-3659 (Linking) VI - 352 DP - 2022 Dec TI - Improving the circulation time and renal therapeutic potency of extracellular vesicles using an endogenous ligand binding strategy. PG - 1009-1023 LID - S0168-3659(22)00761-1 [pii] LID - 10.1016/j.jconrel.2022.11.017 [doi] AB - 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. CI - Copyright (c) 2022 Elsevier B.V. All rights reserved. FAU - Liu, Shuyun AU - Liu S AD - NHC Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, Frontiers Science Center for Disease-related Molecular Network, West China Hospital of Sichuan University, Chengdu, China. FAU - Lv, Ke AU - Lv K AD - NHC Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, Frontiers Science Center for Disease-related Molecular Network, West China Hospital of Sichuan University, Chengdu, China. FAU - Wang, Yizhuo AU - Wang Y AD - NHC Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, Frontiers Science Center for Disease-related Molecular Network, West China Hospital of Sichuan University, Chengdu, China. FAU - Lou, Peng AU - Lou P AD - NHC Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, Frontiers Science Center for Disease-related Molecular Network, West China Hospital of Sichuan University, Chengdu, China. FAU - Zhou, Pingya AU - Zhou P AD - NHC Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, Frontiers Science Center for Disease-related Molecular Network, West China Hospital of Sichuan University, Chengdu, China. FAU - Wang, Chengshi AU - Wang C AD - NHC Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, Frontiers Science Center for Disease-related Molecular Network, West China Hospital of Sichuan University, Chengdu, China; Department of Endocrinology and Metabolism, Center for Diabetes and Metabolism Research, West China Hospital of Sichuan University, Chengdu, China. FAU - Li, Lan AU - Li L AD - NHC Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, Frontiers Science Center for Disease-related Molecular Network, West China Hospital of Sichuan University, Chengdu, China. FAU - Liao, Guangneng AU - Liao G AD - Animal Center, West China Hospital of Sichuan University, Chengdu, China. FAU - Zhang, Yong AU - Zhang Y AD - Institutes for Systems Genetics, West China Hospital of Sichuan University, Chengdu, China. FAU - Chen, Younan AU - Chen Y AD - NHC Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, Frontiers Science Center for Disease-related Molecular Network, West China Hospital of Sichuan University, Chengdu, China. FAU - Cheng, Jingqiu AU - Cheng J AD - NHC Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, Frontiers Science Center for Disease-related Molecular Network, West China Hospital of Sichuan University, Chengdu, China. FAU - Lu, Yanrong AU - Lu Y AD - NHC Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, Frontiers Science Center for Disease-related Molecular Network, West China Hospital of Sichuan University, Chengdu, China. FAU - Liu, Jingping AU - Liu J AD - NHC Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, Frontiers Science Center for Disease-related Molecular Network, West China Hospital of Sichuan University, Chengdu, China. Electronic address: liujingping@scu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221116 PL - Netherlands TA - J Control Release JT - Journal of controlled release : official journal of the Controlled Release Society JID - 8607908 RN - 0 (Ligands) RN - 0 (Peptides) RN - 0 (Albumins) SB - IM MH - Mice MH - Animals MH - Ligands MH - *Extracellular Vesicles/metabolism MH - Kidney MH - *Kidney Diseases/drug therapy/metabolism MH - Peptides/metabolism MH - Albumins/metabolism OTO - NOTNLM OT - Albumin-binding OT - Circulation time OT - Drug delivery OT - Extracellular vesicle OT - Kidney diseases COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/11/15 06:00 MHDA- 2022/12/07 06:00 CRDT- 2022/11/14 19:25 PHST- 2022/08/15 00:00 [received] PHST- 2022/10/19 00:00 [revised] PHST- 2022/11/07 00:00 [accepted] PHST- 2022/11/15 06:00 [pubmed] PHST- 2022/12/07 06:00 [medline] PHST- 2022/11/14 19:25 [entrez] AID - S0168-3659(22)00761-1 [pii] AID - 10.1016/j.jconrel.2022.11.017 [doi] PST - ppublish SO - J Control Release. 2022 Dec;352:1009-1023. doi: 10.1016/j.jconrel.2022.11.017. Epub 2022 Nov 16.