Carbamoylated Guanidine-Containing Polymers for Non-Covalent Functional Protein Delivery in Serum-Containing Media

Despite the high potential of controlling cellular processes and treating various diseases by intracellularly delivered proteins, current delivery systems exhibit poor efficiency due to poor serum stability, cellular entry, and cytosolic availability of proteins. Here, we report a novel functional group, phenyl carbamoylated guanidine (Ph-CG), that greatly enhances the delivery efficiency to various types of cells. Owing to the substantially lowered pK_a , the hydrophobic Ph-CG offers optimized inter-macromolecular interactions via enhanced hydrogen-bonding and hydrophobic interactions. The coplanarity of Ph-CG also leads to the better intracellular entry of protein complexes. Intracellularly delivered apoptosis-inducing enzymes and antibodies significantly induce cell viability inhibitions in a serum-containing medium. The newly developed Ph-CG can be introduced to various existing carriers, leading to the realization of future therapeutic protein delivery.