Exosomes have been increasingly investigated for their potential use of drug delivery. Based on many years’ experience in exosome research and manipulation, Creative Biolabs is now combining the highly versatile delivery capabilities of exosomes with targeting technology and sophisticated biomolecular engineering approaches, to facilitate the development of nanoparticles for drug delivery and vaccine development. Especially, we are committed to offering the first-rate services of exosome targeting.
Exosomes secreted by various cell types are sphere-shaped structures with a bilayer of lipids. They are composed of various types of lipids and proteins derived from the parent cells from which the exosome is formed. Several studies have shown that exosomes intrinsically express some lipids and cell adhesion molecules and ligands naturally targeting certain types of recipient cells. This suggests that exosomes possess natural targeting ability based on donor cells and act as an efficient tool for targeting delivery. For example, exosomes separated from neuroblastoma intrinsically express glycosphingolipid glycan groups that are able to bind to the aggregates of amyloid-β in the brain, and thus provide a potential strategy for Alzheimer's disease treatment. Besides, exosomes targeting to specific tissues can also be achieved by engineering. The target peptides can be displayed on the surface of exosomes through fusion of the ligands/homing peptides with one of the transmembrane proteins (Lactadherin, lysosomeassociated membrane protein-2b (LAMP-2b), and platelet-derived growth factor receptors (PDGFRs)) that are proven to be enriched in exosome compartment.
Fig.1 Production, harvest, and re-administration of targeted self-exosomes for gene delivery. (Alvarez-Erviti, 2011)
In order to achieve exosome targeting, ligands need to be displayed on the surface of exosomes. Biological ligands, however, are general large molecules. These ligands are fused with exosome-associated transmembrane protein may affect the expression, transporting, or the correct folding of the fusion proteins thereby affecting their proper surface display. While core ligand fragment/homing peptides can be displayed on the surface of exosomes in an easy and efficient way. Hence, it is necessary to identify the core ligand fragments for known receptors or homing peptides for unknown receptors, which will facilitate exosome target delivery. Phage display is a useful and popular method for identification of core ligand fragments and homing peptides. Core ligand fragments can be identified by phage display of fragmented open reading frame (ORF) library of a pre-propeptide and followed by in vitro biopanning on cells containing cognate receptors. Homing peptides, usually synthetic peptides, can be discovered by phage display of commercially available peptide phage library, followed by in vitro biopanning to select peptides binding to known cognate receptors, and by in vivo biopanning to find homing peptides binding to unknown receptors.
The most popular strategy for exosome targeting is to display a ligand or a homing peptide specific to target recipient cells on the surface of exosomes. The general process includes several steps:
It is available for exosome targeting via constructing a lentivirus vector with an exosome targeting component. Creative Biolabs has found an exosome targeting peptide which can be incorporated into cloning lentivectors with multiple cloning site for interested proteins fusion. Thus, these lentivectors have the capacity of delivering the interested proteins into exosomes.
Creative Biolabs is a word-leading services provider in exosome research and applications. We are committed to offering the best exosome targeting services for global customers via exosome display and targeting exosome lentivirus vector construction. In addition to exosome target delivery, exosome labeling and cargo loading into exosome are also available in Creative Biolabs. Please contact us for more information if you are interested in any of our services.