Nanomedicine: Nanotechnology, Biology and Medicine
Volume 8, Issue 2 , Pages 204-211, February 2012

Gold-doxorubicin nanoconjugates for overcoming multidrug resistance

  • Yan-Juan Gu, PhD

      Affiliations

    • Department of Biology and Chemistry, The City University of Hong Kong, Kowloon, Hong Kong, China
    • These two authors contributed equally to this work.
    • ,
  • Jinping Cheng, PhD

      Affiliations

    • Department of Biology and Chemistry, The City University of Hong Kong, Kowloon, Hong Kong, China
    • These two authors contributed equally to this work.
    • ,
  • Cornelia Wing-Yin Man, PhD

      Affiliations

    • Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China
    • ,
  • Wing-Tak Wong, PhD

      Affiliations

    • Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China
    • ,
  • Shuk Han Cheng, PhD

      Affiliations

    • Department of Biology and Chemistry, The City University of Hong Kong, Kowloon, Hong Kong, China
    • Corresponding Author InformationCorresponding author.

Received 28 September 2010; accepted 5 June 2011. published online 27 June 2011.

Abstract 

Multidrug resistance (MDR) is a major clinical obstacle to the success of cancer chemotherapy. Here we developed a gold-doxorubicin (DOX) nanoconjugates system to overcome MDR. Gold nanoparticles (AuNPs) were first PEGylated as Au-PEG-NH2, and DOX was then grafted onto AuNPs via a cleavable disulfide linkage (Au-PEG-SS-DOX). Confocal images revealed that the extent of intracellular uptake of Au-PEG-SS-DOX was greater than that of free DOX in the MDR cells, and inductively coupled plasma mass spectroscopy analysis further confirmed that AuNPs significantly increased the level of drug accumulation in MDR cells at a nanoparticles dose greater than 15 μM. The cytotoxicity study demonstrated that the Au-PEG-SS-DOX nanoconjugates system efficiently released the anticancer drug DOX and enhanced its cytotoxicity against MDR cancer cells. This study highlights the potential of using AuNPs for overcoming of MDR in cancer chemotherapy.

From the Clinical Editor

This study demonstrates that gold nanoparticles can be successfully applied to overcome MDR in cancer chemotherapy.

Graphical Abstract 

Gold-doxorubicin nanoconjugates were developed by grafting doxorubicin (DOX) onto polyethylene glycol (PEG)-modified gold (Au) nanoparticles (Au-NPs) via cleavable disulfide (SS) linkage. The Au-PEG-SS-DOX nanoconjugates exhibited higher intracellular uptake and greatly enhanced cytotoxicity for multidrug-resistant cells HepG2-R compared to free DOX. This study highlights the potential of using Au-NPs for overcoming multidrug resistance in cancer chemotherapy.

Key words: Gold nanoparticles, Doxorubicin, Multidrug resistance, Chemotherapy

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 This study was supported by a grant from the Research Grants Council of the Hong Kong SAR, China (Project No. CityU 160108) and a Research Scholarship to Y-J. Gu from the CityU Research Scholarship Enhancement Scheme.

PII: S1549-9634(11)00258-9

doi:10.1016/j.nano.2011.06.005

Nanomedicine: Nanotechnology, Biology and Medicine
Volume 8, Issue 2 , Pages 204-211, February 2012

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