Catechol-Based Polymers with High Efficacy in Cytosolic Protein Delivery

Polymers have been widely proposed as carriers for cytosolic protein delivery despite multiple barriers such as protein binding, cell internalization, and endosome escape during cytosolic delivery. Inspired by the strong binding affinity of natural polyphenols with proteins and cell membranes, herein we propose polyphenol modification to improve the efficacy of the protein delivery of cationic polymers. Catecholmodified dendrimers with balanced hydrophobic and hydrogen-bonding interactions show the highest efficacy for various cargo proteins and peptides while the pyrogallol-grafted ones exhibit the lowest efficacy due to increased ligand hydrophilicity. The catechol-based polymers efficiently deliver various bioactive proteins into the cytosol of live cells, exerting biofunctions after intracellular release, and successfully transmitting alpha-chymotrypsin into tumor cells in vivo to inhibit tumor growth. This study proves that polycatechols can serve as a family of highly efficient carriers for delivery of macromolecular biopharmaceuticals. [GRAPHICS]

Automated summary

This study demonstrates that polyphenols can serve as highly efficient carriers for the delivery of macromolecular biopharmaceuticals. Catechol-modified dendrimers show the highest efficacy for protein delivery, while pyrogallol-grafted ones have the lowest efficacy due to increased hydrophilicity. These catechol-based polymers efficiently deliver bioactive proteins into the cytosol of live cells and have the potential to inhibit tumor growth in vivo.