부산대학교 도서관

Antibodies are being increasingly used for therapeutic purposes due to their remarkable target specificityand affinity. However, currently available antibody therapies are restricted to target proteins in the outercell membrane or in the extracellular fluids because of the lack of technologies for effective intracellulardelivery of antibodies. Here, we report an efficient and versatile intracellular antibody delivery system. This system is based on gold nanoparticles (AuNPs) conjugated with DNA aptamers (Apt) against theFc region of IgG (AuNP-AptIgG), allowing to load any antibodies onto the AuNP-AptIgG by simple mixing. This AuNP-AptIgG-Ab platform was effective for cytosolic delivery of antibodies to clinically importantmutant proteins via scavenger receptors and caveolae-mediated endocytosis. Specifically, cancer cellsexpressing BRAFV600E, a variant of BRAF identified in numerous types of cancers, exhibited reduced cellviability by 70% when BRAFV600E antibodies were intracellularly delivered using the AuNP-AptIgG(AuNP-AptIgG-aBRAFV600E). In addition, subcutaneous injection of AuNP-AptIgG-aBRAFV600E into in vivoxenografted melanoma tumors expressing BRAFV600E resulted in both inhibition of proliferation andinduction of apoptosis, leading to tumor regression in mice. Thus, our findings indicate that the AuNPAptIgG-Ab system can serve as a promising platform for effective intracellular delivery of antibodies fortherapeutic purposes.