Epidermal growth factor-ferritin H-chain nanoparticles as nanocarrier of doxorubicin for overcoming drug resistance in human breast cancer cells

摘要

The emergence of drug-resistant cancer cells together with the side effects of chemotherapy agents are the major obstacle in cancer treatment. We focused on providing a new pattern of protein-based nanoparticle as drug delivery system. FTH1 is a kind of protein that exist in human body which has high bio-safety while EGFR is overexpressed in many cancer cells and it has been used as therapeutic target for cancer treatment. Thus, we used genetic methods for integrating EGF onto the surface of FTH1 and found out a more simple way to express the fusion proteins. To enhance the loading capacity, we first inserted a linker containing more sulfydryl sites (cysteine) into EGF-FTH1 and then adopted chemistry way to covalent bonding the doxorubicin to the nanoparticles. It was found that 72 of DOX molecular could be loaded to one nanoparticle, in vitro they could be released from the nanoparticles at pH5.0. These results demonstrate that the DOX/EGF-XCys-FTHl could be a very promising drug delivery system.