Photoenhanced cytosolic protein delivery based on a photocleavable group-modified dendrimer

Numerous recently developed therapies have highlighted the advantages of using proteins as therapeutics. However, in many protein delivery systems, the complicated carrier designs, low loading content, and off-targeting effects have limited their clinical applications. Here we report a photoresponsive protein-binding moiety and use it to prepare a simple nanoscale protein delivery system with high delivery efficiency and photoenhanced cellular uptake of proteins. The carrier was prepared by modifying a photocleavable molecule, DEACM, onto the surface of a cationic dendrimer, poly(amidoamine). DEACM simultaneously contributed to protein binding, self-assembly, and photocontrollability of the system. The multi-functional DEACM enabled the simplicity of the protein delivery system, which does not require complex organic synthesis or protein modification. The high delivery efficiency, high serum tolerance, and photoenhanced cellular uptake have been proved with functional proteins, presenting the potential for delivering protein therapeutics.