Nitrilotriacetic acid-end-functionalized polycaprolactone as a template for polymer–protein nanocarriers

Diverse polymer–protein nanostructures were introduced as promising platforms for biomedical applications based on their unification of biocompatibility, the bespoke functionalities of proteins, and the structural integrity of polymers. Previously, the polymer-templated protein nanoball (PTPNB) system with Ni2+-nitrilotriacetic acid-end-functionalized polystyrene (Ni2+-NTA-PS) and His6-GFP was reported. These synthesized nanostructures maintained a high protein activity and protein orientation through a soft and strong specific Ni2+-NTA/histidine synergy between the protein and the polymer. However, the toxicity of polystyrene (PS) was a major limitation of the PTPNB system for biomedical applications. Herein, biocompatible polymer–protein nanocarriers were developed by synthesizing nickel-complexed nitrilotriacetic acid-end-functionalized polycaprolactone (Ni2+-NTA-PCL). The potentiality of the current system was the preparation of polymer–protein hybrid nanocarriers with the loaded doxorubicin (DOX) in a one-pot process. Finally, the capability of DOX-loaded GFP/PCL as a therapeutic vehicle was verified by the cellular internalization and cytotoxicity test with neuroblastoma SH-SY5Y cells.