Nanomedicine: Nanotechnology, Biology and Medicine
Volume 6, Issue 2 , Pages 201-209 , April 2010

Radioactive gold nanoparticles in cancer therapy: therapeutic efficacy studies of GA-198AuNP nanoconstruct in prostate tumor–bearing mice

  • Nripen Chanda, PhD

      Affiliations

    • Department of Radiology, University of Missouri, Columbia, Missouri, USA
    • ,
  • Para Kan, MS

      Affiliations

    • Department of Chemistry, University of Missouri, Columbia, Missouri, USA
    • ,
  • Lisa D. Watkinson, MS

      Affiliations

    • Departments of Medical Pharmacology and Physiology, and of Veterinary Medicine, and Harry S. Truman Veterans Administration Medical Center, University of Missouri, Columbia, Missouri, USA
    • ,
  • Ravi Shukla, PhD

      Affiliations

    • Department of Radiology, University of Missouri, Columbia, Missouri, USA
    • ,
  • Ajit Zambre, PhD

      Affiliations

    • Department of Radiology, University of Missouri, Columbia, Missouri, USA
    • ,
  • Terry L. Carmack, MS

      Affiliations

    • Departments of Medical Pharmacology and Physiology, and of Veterinary Medicine, and Harry S. Truman Veterans Administration Medical Center, University of Missouri, Columbia, Missouri, USA
    • ,
  • Hendrik Engelbrecht, PhD

      Affiliations

    • Missouri University Research Reactor, University of Missouri, Columbia, Missouri, USA
    • ,
  • John R. Lever, PhD

      Affiliations

    • Departments of Medical Pharmacology and Physiology, and of Veterinary Medicine, and Harry S. Truman Veterans Administration Medical Center, University of Missouri, Columbia, Missouri, USA
    • ,
  • Kavita Katti, BS

      Affiliations

    • Department of Radiology, University of Missouri, Columbia, Missouri, USA
    • ,
  • Genevieve M. Fent, DVM

      Affiliations

    • Departments of Medical Pharmacology and Physiology, and of Veterinary Medicine, and Harry S. Truman Veterans Administration Medical Center, University of Missouri, Columbia, Missouri, USA
    • ,
  • Stan W. Casteel, DVM, PhD

      Affiliations

    • Departments of Medical Pharmacology and Physiology, and of Veterinary Medicine, and Harry S. Truman Veterans Administration Medical Center, University of Missouri, Columbia, Missouri, USA
    • ,
  • C. Jeffrey Smith, PhD

      Affiliations

    • Department of Radiology, University of Missouri, Columbia, Missouri, USA
    • Departments of Medical Pharmacology and Physiology, and of Veterinary Medicine, and Harry S. Truman Veterans Administration Medical Center, University of Missouri, Columbia, Missouri, USA
    • Missouri University Research Reactor, University of Missouri, Columbia, Missouri, USA
    • ,
  • William H. Miller, PhD

      Affiliations

    • Missouri University Research Reactor, University of Missouri, Columbia, Missouri, USA
    • ,
  • Silvia Jurisson, PhD

      Affiliations

    • Department of Chemistry, University of Missouri, Columbia, Missouri, USA
    • Nuclear Science and Engineering Institute, University of Missouri, Columbia, Missouri, USA
    • Department of Nuclear Engineering, University of Missouri, Columbia, Missouri, USA
    • ,
  • Evan Boote, PhD

      Affiliations

    • Department of Radiology, University of Missouri, Columbia, Missouri, USA
    • ,
  • J. David Robertson, PhD

      Affiliations

    • Department of Chemistry, University of Missouri, Columbia, Missouri, USA
    • Missouri University Research Reactor, University of Missouri, Columbia, Missouri, USA
    • Nuclear Science and Engineering Institute, University of Missouri, Columbia, Missouri, USA
    • Department of Nuclear Engineering, University of Missouri, Columbia, Missouri, USA
    • ,
  • Cathy Cutler, PhD

      Affiliations

    • Department of Chemistry, University of Missouri, Columbia, Missouri, USA
    • Missouri University Research Reactor, University of Missouri, Columbia, Missouri, USA
    • Nuclear Science and Engineering Institute, University of Missouri, Columbia, Missouri, USA
    • Department of Nuclear Engineering, University of Missouri, Columbia, Missouri, USA
    • ,
  • Marina Dobrovolskaia, PhD

      Affiliations

    • Nanotechnology Characterization Laboratory, SAIC-Frederick, National Cancer Institute at Frederick, Frederick, Maryland, USA
    • ,
  • Raghuraman Kannan, PhD

      Affiliations

    • Department of Radiology, University of Missouri, Columbia, Missouri, USA
    • Nanoparticle Biochem, Inc., Columbia, Missouri, USA
    • Corresponding Author InformationCorresponding author: Department of Radiology, University of Missouri–Columbia, Columbia, MO 65211, USA.
    • ,
  • Kattesh V. Katti, PhD, DSc, FRSC

      Affiliations

    • Department of Radiology, University of Missouri, Columbia, Missouri, USA
    • Missouri University Research Reactor, University of Missouri, Columbia, Missouri, USA
    • Nanoparticle Biochem, Inc., Columbia, Missouri, USA
    • Corresponding Author InformationCorresponding author: Department of Radiology, University of Missouri–Columbia, Columbia, MO 65211, USA.

Received 9 September 2009 ,Accepted 3 November 2009.

  • Image Result

    Physicochemical characterization of gum arabic glycoprotein–functionalized gold nanoparticles (GA-AuNPs). (A) Schematic representation of GA-198AuNPs. (B) Dynamic light scattering spectra representing

    Physicochemical characterization of gum arabic glycoprotein–functionalized gold nanoparticles (GA-AuNPs). (A) Schematic representation of GA-198AuNPs. (B) Dynamic light scattering spectra representing hydrodynamic sizes of GA-AuNPs suspended in deionized water (stock), normal saline, and phosphate-buffered saline (PBS). (C) Zeta potential (ZP) of GA-AuNPs.

  • Image Result
    Biocompatibility of surrogate GA-AuNPs. (A) Hemocompatibility assay showing the nonhemolytic nature of GA-AuNPs, wherein amounts of total blood hemoglobin in negative control (NC; 4% polyethylene glyc

    Biocompatibility of surrogate GA-AuNPs. (A) Hemocompatibility assay showing the nonhemolytic nature of GA-AuNPs, wherein amounts of total blood hemoglobin in negative control (NC; 4% polyethylene glycol solution) and in test samples were below the lower limit of quantification (BLOQ) at two different GA-AuNP subtoxic concentrations tested. Triton X-100 was used as a positive control (PC) for hemolysis. (B) Western blot showing qualitative complement activation and subsequent C3 cleavage in PC but not in NC and the three independent replicates of complement proteins exposed to GA-AuNPs (lanes 1, 2, and 3).

  • Image Result
    Platelet aggregation in the presence of (A) GA-AuNPs and of (B) collagen and GA-AuNPs. PBS was used as negative control (NC), and collagen served as positive control (PC). Platelet aggregation ≥20% wa

    Platelet aggregation in the presence of (A) GA-AuNPs and of (B) collagen and GA-AuNPs. PBS was used as negative control (NC), and collagen served as positive control (PC). Platelet aggregation ≥20% was considered positive.

  • Image Result
    Tumor therapy using GA-198AuNPs. (A) Therapeutic efficacy of GA-198AuNPs in prostate tumor–bearing SCID mice. Subcutaneous tumors were generated in SCID mice by PC-3 engraftment. Mice bearing palpable

    Tumor therapy using GA-198AuNPs. (A) Therapeutic efficacy of GA-198AuNPs in prostate tumor–bearing SCID mice. Subcutaneous tumors were generated in SCID mice by PC-3 engraftment. Mice bearing palpable tumors were randomized for treatment (n = 7) and control (n = 7) groups followed by intratumoral (IT) injections of GA-198AuNPs (408 μCi per animal) or DPBS, respectively. Graph represents mean tumor volume following 30 days of treatment. (B) TEM image showing uptake of GA-AuNPs in prostate cancer cells.

  • Image Result
    Comparison of blood parameters including (A) red blood cells, (B) white blood cells, (C) platelets, and (D) lymphocytes counts between the treatment and control groups with baseline levels obtained fr

    Comparison of blood parameters including (A) red blood cells, (B) white blood cells, (C) platelets, and (D) lymphocytes counts between the treatment and control groups with baseline levels obtained from a third group of SCID mice that received no manipulations (normal).

 This research was supported by grants from the National Institutes of Health–National Cancer Institute under the Cancer Nanotechnology Platform Program: 5R01CA119412-01, NIH-1R21CA128460-01, NIH-SBIR-Contract No. 241, and University of Missouri Research Board Program: C8761 RB 06-030.

PII: S1549-9634(09)00252-4

doi: 10.1016/j.nano.2009.11.001

Nanomedicine: Nanotechnology, Biology and Medicine
Volume 6, Issue 2 , Pages 201-209 , April 2010

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