LAUSR

Cytosolic protein delivery is critical for the development of protein-based therapeutics. However, an efficient and robust carrier that can deliver native proteins without biological or chemical modifications into cells is highly desired. Here, we developed a guanidinium-rich polymer consisting of a cationic polymer scaffold modified with both phenyl and biguanide moieties. The polymer showed much higher protein binding affinity and endocytosis and reduced cytotoxicity compared to a control polymer by replacing the biguanide with monoguanide moieties. The guanidinium-rich polymer is capable of transporting proteins with various molecular weights and charge properties into the cytosol of living cells efficiently, while maintaining their bioactivities. This study permits the development of cationic polymers modified with phenylbiguanide moieties for efficient intracellular protein delivery.