Intracellular delivery of immunoglobulin G at nanomolar concentrations with domain Z-fused multimeric α-helical cell penetrating peptides

Autor: Hyung Ho Lee, Jae Hoon Oh, So-Hyun Park, Kyungjin Min, Seung-Eun Chong, Joon Hyung Ahn, Sejong Choi, Yan Lee, Jaehoon Yu, Dahyun Chun
Rok vydání: 2020
Předmět:
Zdroj: Journal of controlled release : official journal of the Controlled Release Society. 330
ISSN: 1873-4995
Popis: A new vehicle is designed for the intracellular delivery of antibodies at nanomolar concentrations by combination of domain Z, a small affibody with strong binding affinity to Fc regions of immunoglobulin G (IgG), and the multimers of LK sequences, α-helical cell penetrating peptides (CPP) with powerful cell penetrating activities. Domain Z and multimeric LK are fused together to form LK-domain Z proteins. The LK-domain Z can bind with IgG at a specific ratio at nanomolar concentrations by simple mixing. The IgG/LK-domain Z complexes can successfully penetrate live cells at nanomolar concentration and the delivery efficiency is strongly dependent upon the concentrations of IgG/LK-domain Z complex as well as the species and subclasses of IgGs. The IgG/LK-domain Z complexes penetrate cells via ATP-dependent endocytosis pathway and the majority of delivered IgG seems to escape endosome to cytosol. Remarkably, the delivered IgGs are able to control the targeted intracellular signaling pathway as shown in the down-regulation of pro-survival genes by the delivery of anti-NF-κB using an LK-domain Z vehicle with a cathepsin B-cleavable linker between the LK sequence and domain Z. The simple but very efficient intracellular delivery method of antibodies at nanomolar concentrations is expected to facilitate profound understanding of cell mechanisms and development of new future therapeutics on the basis of intracellular antibodies.
Databáze: OpenAIRE
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