Surface functionalization of exosomes for target-specific delivery and in vivo imaging & tracking: Strategies and significance

Exosomes are natural nanovesicles excreted by many cells for intercellular communication and for transfer of materials including proteins, nucleic acids and even synthetic therapeutic agents. Surface modification of exosomes imparts additional functionality to the exosomes to enable site specific drug delivery and in vivo imaging and tracking and is an emerging area in drug delivery research. The present review focuses upon these modifications on the exosomal surface, the chemistry involved and their impact on targeted drug delivery for the treatment of brain, breast, lung, liver, colon tumors and, heart diseases and for understanding their in vivo fate including their uptake mechanisms, pharmacokinetics and biodistribution. The specific exosomal membrane proteins such as tetraspanins (CD63, CD81, CD9), lactadherin (LA), lysosome associated membrane protein-2b (Lamp-2b) and, glycosyl-phosphatidyl-inositol (GPI) involved in functionalization of exosome surface have also been discussed along with different strategies of surface modification like genetic engineering, covalent modification (click chemistry and metabolic engineering of parent cells of exosomes) and non-covalent modification (multivalent electrostatic interactions, ligand-receptor interaction, hydrophobic interaction, aptamer based modification and modification by anchoring CP05 peptide) along with optical (fluorescent and bioluminescent) and radioactive isotope labelling techniques of exosomes for imaging purpose.