Boronate Building Blocks for Intracellular Protein Delivery

Intracellular protein delivery plays a critical role in the development of biotherapeutics and biotechnologies, yet it is hampered by a number of factors including protein binding, cellular uptake, endosomal escape, and protein release. Boronate building blocks, which are frequently employed to create effective protein delivery systems, have shown significant promise in overcoming these limitations thanks to their versatile reactivities and stimuli-responsive property. Boronate ligands transport conjugated proteins into the cytosol via receptor-mediated endocytosis by forming reversible boronate disaster bonds with carbohydrates like sialic acid on the cell surface. Additionally, boronate modification gives cargo proteins extra binding sites for forming complexes with nanocarriers. After internalization, boronate-tagged proteins are released from their carriers in response to endolysosomal acidity, reactive oxygen species, and adenosine triphosphate, and sometimes transport into the nucleus via the importin alpha/beta pathway. Besides, boronate ligands are directly decorated on nanocarriers to enhance their binding affinity to native proteins via nitrogen-boron coordination. Owing to these promising features, various supramolecular and dynamic nanoassemblies are constructed based on boronate building blocks for efficient intracellular protein delivery.

Automated summary

Intracellular protein delivery is crucial for biotherapeutics and biotechnologies but faces challenges in terms of protein binding, cellular uptake, endosomal escape, and protein release. Boronate building blocks have shown promise in overcoming these limitations due to their versatile reactivities and stimuli-responsive property. Boronate ligands transport proteins into the cytosol via receptor-mediated endocytosis and can also enhance binding to native proteins on nanocarriers.