Abstract: Disclosed are lung-targeted extracellular vesicles (EVs) loaded with an anti-inflammatory cargo, as well as compositions, systems, and methods for making same. The disclosed EVs can contain a lung targeted ligand, such as a fusion protein containing a lung targeting moiety. Also disclosed is a composition comprising an EV containing the disclosed fusion protein. In some embodiments, the EV is loaded with an anti-inflammatory cargo. Also disclosed is an EV-producing cell engineered to produce the disclosed EVs. Also disclosed is a method for making the disclosed EVs that involves culturing the disclosed EV-producing cells under conditions suitable to produce EVs.