Gold Nanoparticles Enhance the Anti-Leukemia Action of a 6-Mercaptopurine Chemotherapeutic Agent

Abstract

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.

Cellular Uptake, Intracellular Trafficking and Biological Responses of Gold Nanoparticles

“…molecules in a straightforward way; Moreover, GNPs possess unique optical properties, in particular the surface plasmon resonance. All these properties make GNPs very available in gene delivery and intracellular regulation, 38,55 hyperthermia therapy, 4,56 and biosensing using optical and electronic approaches. [6][7][8]57 Recent studies have reinforced the concept that size, shape and surface modification, and charge are critical factors for materials properties.…”

Differential Interactions of Falcarinol Combined with Anti-Tumour Agents on Cellular Proliferation and Apoptosis in Human Lymphoid Leukaemia Cell Lines

“…6-Mercaptopurine (6-MP) is an immunosuppressive drug used to treat Leukaemia and lymphoma particularly childhood lymphoblastic Leukaemia (CLL) [33,34]. 6-MP inhibits purine nucleotide metabolism and synthesis which leads to dysfunctional synthesis and function of RNA and DNA [33].…”

“…6-MP inhibits purine nucleotide metabolism and synthesis which leads to dysfunctional synthesis and function of RNA and DNA [33]. The DNA and RNA damage that results triggers activation of intrinsic apoptosis via p53.…”

“…The DNA and RNA damage that results triggers activation of intrinsic apoptosis via p53. However, because of its severe side effects including inhibition of normal haematopoiesis which can lead to increased risk of infection, anaemia and reduced blood clotting and bleeding, the use of this therapeutic strategy is problematic [33]. As such the use of dual therapies which could reduce the chemotherapy dose used, and thus lead to reduced side effects would be beneficial [35].…”

On the application potential of gold nanoparticles in nanoelectronics and biomedicine

“…the watersoluble derivative of Au 55 , revealed an even higher toxicity than cisplatin, as demonstrated for different cell lines (Tsoli et al 2005), the key question is which parameters influence the impact of AuNPs on the viability of cells, i.e. for intracellular gene regulation (Rosi et al 2006), chemotherapy (Podsiadlo et al 2008) or drug delivery (Han et al 2007a,b), and consequently the number of publications dedicated to toxicity has increased drastically (Connor et al 2005;Nel et al 2006;Pan et al 2007;Boisselier & Astruc 2009;El-Ansary & Al-Daihan 2009). …”