Engineered exosomes for the delivery of bioactive cargo are provided. The exosomes incorporate a tetraspanin transmembrane anchoring scaffold onto the membrane of the exosome. The tetraspanin transmembrane anchoring scaffold has a C-terminal attachment site in the inner-vesicle space of the exosome, a N-terminal attachment site in the inner-vesicle space or the outer-vesicle space, and/or a loop attachment site in the outer-vesicle space. Peptides can be attached to the different attachments sites in any form or combination. Tetrapanins naturally anchor on the exosome membrane, are biocompatible, and allow for robust loading and delivery of bioactive cargos in mammalian system.
