Autophagy inhibitors enhance biomolecular delivery efficiency of extracellular vesicles

Yuanyuan Zhang; Meijuan Huang; Lijun Jiang; Tongjuan Li; Jue Wang; Lei Zhao; Jianfeng Zhou

doi:10.1016/j.bbrc.2022.03.006

Autophagy inhibitors enhance biomolecular delivery efficiency of extracellular vesicles

Biochem Biophys Res Commun. 2022 May 7:603:130-137. doi: 10.1016/j.bbrc.2022.03.006. Epub 2022 Mar 2.

Authors

Yuanyuan Zhang¹, Meijuan Huang¹, Lijun Jiang¹, Tongjuan Li¹, Jue Wang¹, Lei Zhao², Jianfeng Zhou¹

Affiliations

¹ Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
² Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: zl103311@tjh.tjmu.edu.cn.

PMID: 35287054
DOI: 10.1016/j.bbrc.2022.03.006

Abstract

In recent years, extracellular vesicles (EVs) were loaded with therapeutic molecules to be delivered to recipient cells, so the possibility of utilizing EVs for drug delivery has been investigated in various models. Nonetheless, most EVs are degraded through the autophagy pathway after being up-taken by recipient cells, resulting in a low delivery efficiency. Here we introduced a strategy to overcome inefficient delivery of EVs. We demonstrated that autophagy inhibitors, used for reducing lysosomal degradation of EVs, enhanced the protein or plasmid DNA delivery efficiency of EVs in recipient cells without influencing the uptake of EVs by recipient cells. Moreover, autophagy inhibitors could also improve gene-editing efficiency of EV-loaded CRISPR/Cas9 system.

Keywords: Autophagy inhibitor; CRISPR/Cas9 system; Delivery efficiency; Extracellular vesicle.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autophagy
Biological Transport
Extracellular Vesicles* / metabolism
Gene Editing
Lysosomes / metabolism