Design of Polymers for Intracellular Protein and Peptide Delivery

Abstract

AbstractCytosolic protein delivery techniques are of great importance for cell biology, biotechnology and protein drug development. The design of carriers with robust efficiency in cytosolic protein delivery is challenging. This account provides a progress report of polymeric carriers for this purpose in our group. During the past years, we have developed several types of functionalized polymers for cytosolic protein and peptide delivery by engineering polymers with ligands such as guanidinium, boronate, coordination ligands and fluoroalkyls. The designed polymers showed improved protein/peptide binding affinities, and successfully delivered various cargo proteins into the cytosol of living cells, while maintaining their bioactivity. In addition, the polymers showed potent efficiencies in the delivery of tumor antigens, therapeutic peptides, toxins and antioxidant proteins in vivo. We hope these polymers could be translated for protein delivery in the treatment of various diseases in the future. What is the most favorite and original chemistry developed in your research group?Fluorinated polymers for cytosolic biomolecule delivery.How do you get into this specific field? Could you please share some experiences with our readers?I get into this field by unexpected discoveries when designing polymeric gene delivery systems. Usually, modification of polymers with hydrophobic ligands yields more efficient gene carriers. Fluoroalkyl ligands wereproposed as one type of hydrophobic candidates in our experiments. Interestingly, the fluorous ligand modified polymers showed unprecedented efficiency in gene delivery. More importantly, the polymers exhibited excellent serum resistance and could achieve high efficiency at extremely low polymer dose. These unexpected discoveries motivated us to investigate the fluorine effect of fluorinated materials in gene, protein and peptide delivery.