Colloidal gold modified with a genetically engineered nitroreductase: toward a novel enzyme delivery system for cancer prodrug therapy.
Directed enzyme prodrug therapy is an extensive area of research in cancer chemotherapy. Although very promising, the current directed approaches are still hampered by inefficient enzyme expression and tumor targeting. This work investigates the viability of using metal nanoparticles as a novel delivery vehicle for prodrug-activating enzymes. Using genetically incorporated amino acid sequences, a nitroreductase from E. coli was directly immobilized onto a 50 nm gold colloid, as confirmed by gel electrophoresis, DLS, and UV-vis spectroscopy. The resulting conjugates showed excellent stability in changing proton and sodium chloride environments, including PBS at 37 °C. Remarkably, the immobilized nitroreductase retained more than 99% activity to the CB1954 prodrug without the need for stabilizers. This work provides the foundation for attaching prodrug-activating enzymes to metal nanoparticles for future use in directed enzyme prodrug therapy.
School of Chemistry, Bangor University, Bangor, Gwynedd, LL57 2DG, Wales, United Kingdom.
Vanessa V
VV
Gwenin
Chris D
CD
Gwenin
Maher
M
Kalaji
D001388:Aziridines / Q000627:therapeutic use*; D003102:Colloids / Q000737:chemistry; D016503:Drug Delivery Systems; D006046:Gold / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy*; D009601:Nitroreductases / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D011355:Prodrugs / Q000627:therapeutic use*; D015202:Protein Engineering; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D012965:Sodium Chloride / Q000737:chemistry
D001388:Aziridines; D003102:Colloids; D011355:Prodrugs; D011994:Recombinant Proteins; D012965:Sodium Chloride; D006046:Gold; C100099:tretazicar; D009601:Nitroreductases