Partial Magneto-Endosomalysis for Cytosolic Delivery of Antibodies

Modulation of protein functions and interactions is the most direct and effective means to intervene in cellular processes and pathogenesis. The majority of the critical intracellular signaling pathways, however, are considered undruggable using small molecules. In this regard, antibodies are superior in structural and functional diversity and are significantly easier to raise compared to the screening of small molecules. Despite these advantages, the uses of antibodies in live cells (either as an imaging agent or as a therapeutic compound) are substantially undermined, only acting on extracellular targets. The inability of targeting intracellular proteins is because of a fundamental issue: antibodies enter cells through endocytosis where the vast majority are trapped in endosomes for degradation. Here, we report a nanoparticle self-assembly strategy enabling antibody endosomal escape. We demonstrate the intracellular bioavailability of antibodies and the preserved binding specificity to their cytosolic targets. This technology is simple and opens exciting opportunities for live-cell imaging, therapeutics development, and cell engineering.