Part:BBa_K1942002:Design

In order to obtain exosomes with tumor-targeting ability, we modified natural exosomes using a tumor-targeting short peptide. Some studies have shown that iRGD, a tumor-penetrating peptide, homes to tumors by strictly binding to αν integrins that are specifically expressed on tumor cells and the endothelium of tumor vessels. Meanwhile, iRGD peptide also own the ability of penetrating tumor tissue against interstitial pressure. When combined with a drug vesicle, iRGD peptide can carry the drug vesicle deep into the extravascular tumor tissue. Lamp2b (lysosomal-associated membrane protein 2b) is a protein found specifically abundant on the surface of exosomes. We connected iRGD to Lamp2b using a glycine-linker to construct our fusion protein and promoted its expression by the cmv promoter, hence, Lamp2b can bring the iRGD peptide to the surface of exosomes. Then the iRGD peptide can guide exosomes to the specific tumor tissue. Through these modifications, exosomes will be conferred on tumor-targeting ability.

Figure 1. RVG-Lamp2b fusion protein modified exosome, with gene specific siRNAs involved inside