A genipin-crosslinked protein–polymer hybrid system for the intracellular delivery of ribonuclease A

BACKGROUND: Therapeutic proteins have been widely used in the treatment of various diseases, and effective carriers are highly required for achieving protein delivery to obtain favorable treatment potency. MATERIALS AND METHODS: A protein–polymer hybrid system was constructed through the genipin-mediated crosslinking of polyethyleneimine with a weight-average molecular weight of 25,000 g/mol (PEI25K) and ribonuclease A (RNase A), namely RGP. RESULTS: The RGP nanoparticles were observed to be easily internationalized in HeLa cells owing to the introduction of positively charged PEI25K, thereby triggering the antiproliferative effects by cleaving RNA molecules in the tumor cells. Moreover, red fluorescence could be obviously visualized in the tumor cells after RGP delivery, which was attributed to the intrinsic characteristics of genipin. CONCLUSION: The protein–polymer hybrid system prepared via the genipin-mediated crosslinking has exhibited potential to be used as a theranostic platform for both in vivo imaging and delivering diverse therapeutic proteins.