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 His(6)-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.