Gold nanoparticles enhance the anti-leukemia action of a 6-mercaptopurine chemotherapeutic agent.
6-mercaptopurine and its riboside derivatives are some of the most widely utilized anti-leukemic and anti-inflammatory drugs. Their short biological half-life and severe side effects limit their use. A new delivery method for these drugs based on 4-5 nm gold nanoparticles can potentially resolve these issues. We have found substantial enhancement of the antiproliferative effect against K-562 leukemia cells of Au nanoparticles bearing 6-mercaptopurine-9-beta-d-ribofuranoside compared to the same drug in typically administered free form. The improvement was attributed to enhanced intracellular transport followed by the subsequent release in lysosomes. Enhanced activity and nanoparticle carriers will make possible the reduction of the overall concentration of the drug, renal clearance, and, thus, side effects. The nanoparticles with mercaptopurine also showed excellent stability over 1 year without loss of inhibitory activity.
Departments of Chemical Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA.
Paul
P
Podsiadlo
Vladimir A
VA
Sinani
Joong Hwan
JH
Bahng
Nadine Wong Shi
NW
Kam
Jungwoo
J
Lee
Nicholas A
NA
Kotov
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005434:Flow Cytometry; D006046:Gold / Q000737:chemistry*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D015122:Mercaptopurine / Q000627:therapeutic use*; D053768:Metal Nanoparticles; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission
D000970:Antineoplastic Agents; D006046:Gold; D015122:Mercaptopurine