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

Chanda, Nripen; Kan, Para; Watkinson, Lisa D.; Shukla, Ravi; Zambre, Ajit; Carmack, Terry L.; Engelbrecht, Hendrik; Lever, John R.; Katti, Kavita; Fent, Genevieve M.; Casteel, Stan W.; Smith, C. Jeffrey; Miller, William H.; Jurisson, Silvia; Boote, Evan; Robertson, J. David; Cutler, Cathy; Dobrovolskaia, Marina; Kannan, Raghuraman; Katti, Kattesh V.

doi:10.1016/j.nano.2009.11.001

« Previous Next »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
- Department of Radiology, University of Missouri, Columbia, Missouri, USA
Para Kan, MS
- Department of Chemistry, University of Missouri, Columbia, Missouri, USA
Lisa D. Watkinson, MS
- 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
- Department of Radiology, University of Missouri, Columbia, Missouri, USA
Ajit Zambre, PhD
- Department of Radiology, University of Missouri, Columbia, Missouri, USA
Terry L. Carmack, MS
- 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
- Missouri University Research Reactor, University of Missouri, Columbia, Missouri, USA
John R. Lever, PhD
- 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
- Department of Radiology, University of Missouri, Columbia, Missouri, USA
Genevieve M. Fent, DVM
- 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
- 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
- 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
- Missouri University Research Reactor, University of Missouri, Columbia, Missouri, USA
Silvia Jurisson, PhD
- 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
- Department of Radiology, University of Missouri, Columbia, Missouri, USA
J. David Robertson, PhD
- 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
- 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
- Nanotechnology Characterization Laboratory, SAIC-Frederick, National Cancer Institute at Frederick, Frederick, Maryland, USA
Raghuraman Kannan, PhD
- Department of Radiology, University of Missouri, Columbia, Missouri, USA
- Nanoparticle Biochem, Inc., Columbia, Missouri, USA
- Corresponding author: Department of Radiology, University of Missouri–Columbia, Columbia, MO 65211, USA.
Kattesh V. Katti, PhD, DSc, FRSC
- 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: Department of Radiology, University of Missouri–Columbia, Columbia, MO 65211, USA.

Received 9 September 2009; accepted 3 November 2009. published online 16 November 2009.

Abstract

Biocompatibility studies and cancer therapeutic applications of nanoparticulate β-emitting gold-198 (¹⁹⁸Au; β_max = 0.96 MeV; half-life of 2.7 days) are described. Gum arabic glycoprotein (GA)–functionalized gold nanoparticles (AuNPs) possess optimum sizes (12–18 nm core diameter and 85 nm hydrodynamic diameter) to target individual tumor cells and penetrate through tumor vasculature and pores. We report the results of detailed in vivo therapeutic investigations demonstrating the high tumor affinity of GA-¹⁹⁸AuNPs in severely compromised immunodeficient (SCID) mice bearing human prostate tumor xenografts. Intratumoral administration of a single dose of β-emitting GA-¹⁹⁸AuNPs (70 Gy) resulted in clinically significant tumor regression and effective control in the growth of prostate tumors over 30 days. Three weeks after administration of GA-¹⁹⁸AuNPs, tumor volumes for the treated animals were 82% smaller as compared with tumor volume of control group. The treatment group showed only transitory weight loss in sharp contrast to the tumor-bearing control group, which underwent substantial weight loss. Pharmacokinetic studies have provided unequivocal evidence for the optimum retention of therapeutic payload of GA-¹⁹⁸AuNPs within the tumor site throughout the treatment regimen with minimal or no leakage of radioactivity to various nontarget organs. The measurements of white and red blood cells, platelets, and lymphocytes within the treatment group resembled those of the normal SCID mice, thus providing further evidence on the therapeutic efficacy and concomitant in vivo tolerance and nontoxic features of GA-¹⁹⁸AuNPs.

From the Clinical Editor

In this study, the biocompatibility and cancer therapeutic applications of glycoprotein (GA) functionalized gold nanoparticles containing b-emitting Au-198 are described in SCID mice bearing human prostate tumor xenografts. The findings of significant therapeutic efficacy, good in vivo tolerance and non-toxic features make these particles ideal candidates for future human applications.

Key words: Radioactive gold nanoparticles, Prostate tumor, Therapeutics, Tumor vasculature, Intratumoral

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

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

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