Disclosed herein are MDSC-targeted extracellular vesicles (EVs) loaded with therapeutic cargo, as well as compositions, systems, and methods for making same. Also disclosed herein is an MDSC-targeting ligand, such as a fusion protein containing an MDSC-targeting moiety. Also disclosed are EVs containing the disclosed fusion protein. In some embodiments, the EV is also loaded with a therapeutic 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.
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