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. (C) 2022 Elsevier Inc. All rights reserved.