ScholarWorks@중앙대학교

초록

Antibodies are being increasingly used for therapeutic purposes due to their remarkable target specificity and affinity. However, currently available antibody therapies are restricted to target proteins in the outer cell membrane or in the extracellular fluids because of the lack of technologies for effective intracellular delivery 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 the Fc 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 important mutant proteins via scavenger receptors and caveolae-mediated endocytosis. Specifically, cancer cells expressing BRAFV600E, a variant of BRAF identified in numerous types of cancers, exhibited reduced cell viability by 70% when BRAFV600E antibodies were intracellularly delivered using the AuNP-AptIgG (AuNP-AptIgG-αBRAFV600E). In addition, subcutaneous injection of AuNP-AptIgG-αBRAFV600E into in vivo xenografted melanoma tumors expressing BRAFV600E resulted in both inhibition of proliferation and induction of apoptosis, leading to tumor regression in mice. Thus, our findings indicate that the AuNP-AptIgG-Ab system can serve as a promising platform for effective intracellular delivery of antibodies for therapeutic purposes. © 2023 The Korean Society of Industrial and Engineering Chemistry

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