Targeted therapeutic delivery using engineered exosomes and its applications in cardiovascular diseases

• Exosomes are natural carriers of signaling molecules including miRNA.
• Membrane proteins including tetraspanins are selectively enriched on membrane of exosomes.
• Homing peptides targeting unknown receptors in vivo can be displayed on the surface of exosomes.
• Surface display of homing peptides can be easily achieved by fusion with tetraspanins using overlapping PCR.
• Engineered exosomes can be loaded with therapeutic miRNAs to realize targeted delivery in vivo.

Exosomes are 30–120 nm membrane bound vesicles secreted naturally by almost all cells and exist in all body fluids. Accumulating evidence has shown that exosomes contain proteins, lipids, DNA, mRNA, miRNA, and lncRNA that can be transferred from producer cells to recipient cells, facilitating cell–cell communication. As the natural carrier of these signal molecules, exosomes possess many other properties such as stability, biocompatibility, biological barrier permeability, low toxicity, and low immunogenicity, which make them an attractive vehicle for therapeutic delivery. How exosomes target recipient cells in vivo remains largely unknown, however, exosomes are selectively enriched in some transmembrane proteins that can be genetically engineered to display ligands/homing peptides on their surface, which confers exosome targeting capability to cells bearing cognate receptors. With the discovery of many peptides homing to diseased tissues or organs through phage display and in vivo biopanning technologies, there is ample opportunity to explore the potential use of exosome for targeted gene therapy. Here, we briefly review exosome biogenesis, mechanisms of exosome-mediated cell–cell communication, and exosome isolation and purification methods, and specifically focus on the emerging exosome targeting technologies.