Demonstration of intracellular trafficking, cytosolic bioavailability, and target manipulation of an antibody delivery platform

Abstract

Intracellular antibody delivery into live cells has significant implications for research and therapeutic applications. However, many delivery systems lack potency due to low uptake and/or endosomal entrapment and understanding of intracellular delivery processes is lacking. Herein, we studied the cellular uptake, intracellular trafficking and targeting of antibodies using our previously developed Hex antibody nanocarrier. We demonstrated Hex-antibodies were internalized through multiple endocytic routes into lysosomes and provide evidence of endo/lysosomal disruption and Hex-antibody release to the cytosol. Cytosolic antibodies retained their bioactivity for at least 24 h. Functional effect of Hex delivered anti-STAT3 antibodies was evidenced by inhibition of nuclear translocation of cytosolic transcription factor STAT3. This study has generated understanding of key steps in the Hex intracellular antibody delivery system and will facilitate the development of effective cytosolic antibody delivery and applications in both the therapeutic and research domains.