Design strategies and application progress of therapeutic exosomes

Abstract

Exosomes have great potential to be drug delivery vehicles due to their natural material transportation properties, intrinsic long-term circulatory capability, and excellent biocompatibility, which are suitable for delivering a variety of chemicals, proteins, nucleic acids, and gene therapeutic agents. However, an effective method of loading specific protein agents into exosomes for absorption by target cells is still lacking. The application potential of exosome is still limited. In this review, we discussed the methods for loading specific treating molecules (proteins, nucleic acids and small chemicals) into exosomes, the design strategies for cell and tissue targeting, and the factors for exosome formation. This review can be used as a reference for further research as well as for the development of therapeutic exosomes.

Keywords: drug carrier; exosome; therapeutic strategy.

Figure 1

Methods of loading specific proteins, nucleic acids and small molecular drugs into engineered exosomes. The specific treating molecules can be loaded into exosomes before or after exosome production through natural or specific packaging.

Figure 2

Design strategies for therapeutic exosome targeting. Targeting is the key to the therapeutic potential of exosomes. It can be improved by selecting the exosome donor cells and the modification of surface molecules on exosomes. AA-PEG: aminoethylanisamide-polyethylene glycol; GPI: glycosylphos-phatidylinositol; RVG: rabies virus glycoprotein; VSVG: vesicular stomatitis virus glycoprotein; A33Ab-US: the surface-carboxyl superparamagnetic iron oxide nanoparticles (US) were coated with A33 antibody, to bind to A33-positive exosomes; iRGD: an αⅤ integrin-specific internalizing peptide; PDGFR TM domain: PDGFR transmembrane domain.