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

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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-β-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.

Citing Articles

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This article has been cited by 8 ACS Journal articles (5 most recent appear below).

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  Mercaptocarborane-Capped Gold Nanoparticles: Electron Pools and Ion Traps with Switchable Hydrophilicity

  Ana M. Cioran, Ana D. Musteti, Francesc Teixidor, Željka Krpetić, Ian A. Prior, Qian He, Christopher J. Kiely, Mathias Brust, and Clara Viñas
  Journal of the American Chemical Society2012 134 (1), 212-221

  • Mercaptocarborane-Capped Gold Nanoparticles: Electron Pools and Ion Traps with Switchable Hydrophilicity

    Ana M. Cioran, Ana D. Musteti, Francesc Teixidor, Željka Krpetić, Ian A. Prior, Qian He, Christopher J. Kiely, Mathias Brust, and Clara Viñas
    Journal of the American Chemical Society2012 134 (1), 212-221

    A simple single-phase method for the preparation of ca. 2 nm gold nanoparticles capped with mercaptocarborane ligands is introduced. The resultant monolayer protected clusters (MPCs) exhibit redox-dependent solubility and readily phase transfer between ...

    Abstract | Full Text HTML | Hi-Res PDF | PDF w/ Links
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  Thiol with an Unusual Adsorption−Desorption Behavior: 6-Mercaptopurine on Au(111)

  E. Pensa, P. Carro, A. A. Rubert, G. Benítez, C. Vericat, and R. C. Salvarezza
  Langmuir2010 26 (22), 17068-17074

  • Thiol with an Unusual Adsorption−Desorption Behavior: 6-Mercaptopurine on Au(111)

    E. Pensa, P. Carro, A. A. Rubert, G. Benítez, C. Vericat, and R. C. Salvarezza
    Langmuir2010 26 (22), 17068-17074

    A multitechnique study of 6-mercaptopurine (6MP) adsorption on Au(111) is presented. The molecule adsorbs on Au(111), originating short-range ordered domains and irregular nanosized aggregates with a total surface coverage by chemisorbed species smaller ...

    Abstract | Full Text HTML | Hi-Res PDF | PDF w/ Links
• 

  Multiple Release Kinetics of Targeted Drug from Gold Nanorod Embedded Polyelectrolyte Conjugates Induced by Near-Infrared Laser Irradiation

  Tsung-Rong Kuo, Vladimir A. Hovhannisyan, Yu-Ching Chao, Shu-Ling Chao, Shu-Jen Chiang, Sung-Jan Lin, Chen-Yuan Dong, and Chia-Chun Chen
  Journal of the American Chemical Society2010 132 (40), 14163-14171

  • Multiple Release Kinetics of Targeted Drug from Gold Nanorod Embedded Polyelectrolyte Conjugates Induced by Near-Infrared Laser Irradiation

    Tsung-Rong Kuo, Vladimir A. Hovhannisyan, Yu-Ching Chao, Shu-Ling Chao, Shu-Jen Chiang, Sung-Jan Lin, Chen-Yuan Dong, and Chia-Chun Chen
    Journal of the American Chemical Society2010 132 (40), 14163-14171

    The conjugates of gold nanorods and the model drug, fluorescein isothiocyanate (FITC), embedded inside polyelectrolytes (GNRs/FITC@PLE) were synthesized to study the release kinetics of FITC under femtosecond near-infrared (NIR) laser irradiation. The ...

    Abstract | Full Text HTML | Hi-Res PDF | PDF w/ Links
• 

  SERS-Active Gold Lace Nanoshells with Built-in Hotspots

  Ming Yang, Ramón Alvarez-Puebla, Hyoung-Sug Kim, Paula Aldeanueva-Potel, Luis M. Liz-Marzán, and Nicholas A. Kotov
  Nano Letters2010 10 (10), 4013-4019

  • SERS-Active Gold Lace Nanoshells with Built-in Hotspots

    Ming Yang, Ramón Alvarez-Puebla, Hyoung-Sug Kim, Paula Aldeanueva-Potel, Luis M. Liz-Marzán, and Nicholas A. Kotov
    Nano Letters2010 10 (10), 4013-4019

    Development of multifunctional drug delivery vehicles with therapeutic and imaging capabilities as well as in situ methods of monitoring of intracellular processes will greatly benefit from a simple method of preparation of plasmonic Au structures with ...

    Abstract | Full Text HTML | Hi-Res PDF | PDF w/ Links
• 

  pH-Induced Aggregation of Gold Nanoparticles for Photothermal Cancer Therapy

  Jutaek Nam, Nayoun Won, Ho Jin, Hyokyun Chung and Sungjee Kim
  Journal of the American Chemical Society2009 131 (38), 13639-13645

  • pH-Induced Aggregation of Gold Nanoparticles for Photothermal Cancer Therapy

    Jutaek Nam, Nayoun Won, Ho Jin, Hyokyun Chung and Sungjee Kim
    Journal of the American Chemical Society2009 131 (38), 13639-13645

    We report a "smart" gold nanoparticle that is designed to aggregate in mild acidic intracellular environments by its hydrolysis-susceptible citraconic amide surface. With a relatively small size of 10 nm, the "smart" gold nanoparticles can be efficiently ...

    Abstract | Full Text HTML | Hi-Res PDF | PDF w/ Links

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