09-07-2012, 10:54 AM
Applications of gold nanoparticles in cancer nanotechnology
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Abstract:
It has been almost 4 decades since the “war on cancer” was declared. It is now
generally believed that personalized medicine is the future for cancer patient management.
Possessing unprecedented potential for early detection, accurate diagnosis, and personalized
treatment of cancer, nanoparticles have been extensively studied over the last decade. In this
review, we will summarize the current state-of-the-art of gold nanoparticles in biomedical
applications targeting cancer. Gold nanospheres, nanorods, nanoshells, nanocages, and surface
enhanced Raman scattering nanoparticles will be discussed in detail regarding their uses in in
vitro assays, ex vivo and in vivo imaging, cancer therapy, and drug delivery. Multifunctionality
is the key feature of nanoparticle-based agents. Targeting ligands, imaging labels, therapeutic
drugs, and other functionalities can all be integrated to allow for targeted molecular imaging
and molecular therapy of cancer. Big strides have been made and many proof-of-principle
studies have been successfully performed. The future looks brighter than ever yet many hurdles
remain to be conquered. A multifunctional platform based on gold nanoparticles, with multiple
receptor targeting, multimodality imaging, and multiple therapeutic entities, holds the promise
for a “magic gold bullet” against cancer.
Introduction
Cancer is the third leading cause of death (after heart disease and stroke) in developed
countries and the second leading cause of death (after heart disease) in the United
States (see http://www.cdc.gov). Studies have shown that there were 10 million new
cases, 6 million deaths, and 22 million people living with cancer worldwide in the
year 2000 (Parkin 2001). These numbers represent an increase of about 22% in incidence
and mortality from that of the year 1990 (Parkin et al 1999; Pisani et al 1999).
It is projected that the number of new cases of all cancers worldwide will be 12.3 and
15.4 million in the year 2010 and 2020, respectively (Parkin 2001). In 2008, a total
of 1,437,180 new cancer cases and 565,650 cancer deaths were estimated to occur in
the United States alone (Jemal et al 2008).
Synthesis of gold nanoparticles
There are many subtypes of gold nanoparticles based on the
size, shape, and physical properties (Figure 2). The earliest
studied gold nanoparticles are gold nanospheres (although not
exactly spherical in a strict sense). Subsequently, nanorods,
nanoshells, and nanocages have all been reported. Another
type of gold-based nanoparticles, with excellent surfaceenhanced
Raman scattering properties (termed “SERS
nanoparticles”), will also be discussed in this review. In the
following text, the term “gold nanoparticle(s)” will refer to
a collection of all these subtypes and the subtype of gold
nanoparticles used in each study will be specifi ed whenever
possible. With continued development in the synthesis
techniques over the last two decades, most of these gold
nanoparticles can now be produced with well-controlled
size distribution, sometimes with stunning precision
(eg, nanocages).
Gold nanospheres
Gold nanospheres (also known as gold colloids) of 2 nm to
over 100 nm in diameter can be synthesized by controlled
reduction of an aqueous HAuCl4 solution using different
reducing agents under varying conditions. The most
commonly used reducing agent is citrate, which can produce
nearly monodisperse gold nanospheres (Turkevich et al 1951;
Frens 1973). The size of the nanospheres can be controlled
by varying the citrate/gold ratio. Generally, smaller amount
of citrate will yield larger nanospheres. The major limitations
of this method are the low yield and the restriction of using
water as the solvent.
Applications of nanoparticles
Nanotechnology has been an extremely hot topic over
the last decade. A simple search of “Nano” in PubMed
returned more than 6000 publications. Two major areas of
nanoparticle applications are material science and biomedicine.
Big strides have been made in the material science
arena. The fact that electronics are getting faster, better,
and smaller each month is a clear and strong evidence for
such achievement. However, applications of nanoparticles
in the biomedical fi eld have not fulfi lled the expectations.
Very few nanoparticle-based agents are in clinical testing
or commercialized for cancer diagnosis or treatment, and
most of them are based on liposomes which were developed
several decades ago. There is still a long way to go before
nanotechnology can truly revolutionize patient care as
many have hoped it would. Next, we will summarize the
progress to date regarding the use of gold nanoparticles for
biomedical applications.
Biomedical applications of gold nanoparticles
Cancer nanotechnology is an interdisciplinary area with
broad potential applications in fi ghting cancer, including
molecular imaging, molecular diagnosis, targeted therapy,
and bioinformatics. The continued development of cancer
nanotechnology holds the promise for personalized oncology
in which genetic and protein biomarkers can be used to diagnose
and treat cancer based on the molecular profi le of each
individual patient. Gold nanoparticles have been investigated
Nanotechnology, Science and Applications 2008:1 21
Gold nanoparticles in cancer
in diverse areas such as in vitro assays, in vitro and in vivo
imaging, cancer therapy, and drug delivery.