Functionalized radioactive gold
nanoparticles in tumor therapy
Raghuraman Kannan,1∗ Ajit Zambre,1 Nripen Chanda,1 Rajesh
Kulkarni,1 Ravi Shukla,1 Kavita Katti,1 Anandhi Upendran,2 Cathy
Cutler,3 Evan Boote1 and Kattesh V. Katti1∗
The development of new treatment modalities that offer clinicians the ability to
reduce sizes of tumor prior to surgical resection or to achieve complete ablation
without surgery would be a significant medical breakthrough in the overall care
and treatment of prostate cancer patients. The goal of our investigation is aimed
at validating the hypothesis that Gum Arabic-functionalized radioactive gold
nanoparticles (GA-198AuNP) have high affinity toward tumor vasculature. We
hypothesized further that intratumoral delivery of the GA-198AuNP agent within
prostate tumor will allow optimal therapeutic payload that will significantly
or completely ablate tumor without side effects, in patients with hormone
refractory prostate cancer. In order to evaluate the therapeutic efficacy of this
new nanoceutical, GA-198AuNP was produced by stabilization of radioactive gold
nanoparticles (198Au) with the FDA-approved glycoprotein, GA. This review
will describe basic and clinical translation studies toward realization of the
therapeutic potential and myriad of clinical applications of GA-198AuNP agent
in treating prostate and various solid tumors in human cancer patients. © 2011 Wiley
Periodicals, Inc.
How to cite this article:
WIREs Nanomed Nanobiotechnol 2012, 4:42–51. doi: 10.1002/wnan.161
INTRODUCTION
Prostate cancer in men is the second deadliest
cancer after lung cancer. Approximately 217,730
men are diagnosed with prostate cancer resulting in
loss of life for 32,050 men.1 Prostate cancer diagnosis
begins either with a digital rectal exam during which
a doctor feels the prostate to check for irregularity or
a blood test to check the level of prostate-specific antigen
(PSA) or both.2,3 Recent studies have shown that
regular PSA screening did not increase the survival
rate over a period of 10 years.4,5 Early detection
of prostate tumor by common imaging modalities
such as ultrasound (US), computer tomography (CT)
is difficult, as the prostate is deep inside the pelvis
and harder to access. These clinical impediments will
∗Correspondence to:
[email protected],
[email protected]1Department of Radiology, University of Missouri, Columbia, MO,
USA 2Nanoparticle Biochem, Inc., Columbia, MO, USA
3Missouri University Research Reactor, University of Missouri,
Columbia, MO, USA
continue to hinder accurate and early detection of
prostate cancer resulting in more cases of androgen
dependent and hormone independent prostate cancers
and thus posing some of the most vexing questions
in medicine.6 The widely used brachy therapy utilize
agents of 50–100 μm in size including 125I or 103Pd
radioactive seeds, and Y-90 immobilized glass
microspheres (Therasphere™) to achieve selective internal
radiation therapy (SIRT).7–9 The limited
natural affinity of these microspheres toward
tumor vasculature coupled with significantly larger
(50–100 μm) sizes as compared to the porosity
of tumor vasculature (150–300 nm) causes limited
retention and significant leakage of therapeutic doses
away from the tumor site. These problems result in
decreased efficacy, acute toxic side effects and lower
tumoricidal activity of brachy therapy agents.
A central goal of chemo or radiation therapy
while treating patients with prostate (and other
solid tumors) cancer is to achieve maximum dose
intensity at the tumor site while managing drugrelated
toxicities to the minimum to non-target
42 © 2011 Wiley Periodicals, Inc. Volume 4, January/February 2012
