EGFR Nanobody-functionalized bovine milk exosomes for target-specific drug delivery

• 1、School of bioengineering, Jiangnan University, Wuxi 214122, China

Abstract：Target-specific delivery of chemotherapy drugs to tumor site is an important path to improve the overall clinical outcomes. In this work, we reported an EGFR-targeted drug delivery system using milk exosomes (mExo) functionalized with EGFR nanobody 7D12. The mExo was first equipped with a glycine-modified membrane inserting molecule NH2-GG-PEG2000-DSPE through its hydrophobic tail, which was further fused with the nanobody 7D12 through a SrtA-mediated enzymatic ligation. The successful construction of 7D12-mExo was confirmed by western blotting analysis, electronic microscope, and dynamic light scattering (DLS). Immunocytochemistry and flow cytometry analysis of 7D12-mExo loaded with the antineoplastic drug Adriamycin (Dox) demonstrated that it can target and deliver dox to cells in response to the expression of EGFR. Finally, the cytotoxicity test showed that 7D12-mExo loaded with Dox was more effective to kill tumor cells with high EGFR expression. Taken together, these results demonstrated that 7D12-fucnationalized mExo as a target-specific delivery system was able to deliver the cargo drug of Dox to EGFR expressing cell, and selectively kill the tumor cells.

Keywords： target-specific delivery milk exosomes target target-specific nanoparticle EGFR 7D12 Dox