[Catalyst 2016] Final

An important factor of GNP therapy is the
efficient targeting and release of remedial
agents at the designated cancerous site.
There are two types of GNP targeting:
passive and active. In passive targeting,
nanoparticles accumulate at a specific
site by physicochemical factors (e.g. size,
molecular weight, and shape), extravasation,
or pharmacological factors. Release can
be triggered by internal factors such as
pH changes or external stimuli such as
application of light. 2 In active targeting,
ligand molecules attached to the surface
of a GNP render it capable of effectively
delivering pharmaceutical agents and large
biomacromolecules to specific cells in the
body.
GOLD NANOPARTICLES IN LOCALIZED
CANCER THERAPY
Hyperthermia
Hyperthermia is a localized cancer therapy
in which cancerous tissue is exposed to high
temperatures to induce cell death. Placing
gold nanoparticles at the site of therapy can
improve the efficiency and effectiveness
of hyperthermia, leading to lower levels of
tumor growth. GNPs aggregated at cancerous
tissues allow intense, localized increases in
temperature that better induce cell death.
In one study on mice, breast tumor tissue
containing aggregated GNPs experienced
a temperature increase 28°C higher than
control breast tumor tissue when subjected
to laser excitation. 9 While the control
tissue had recurring cancerous growth, the
introduction of GNPs significantly increased
the therapeutic temperature of the tumors
and permanently damaged the cancerous
tissue.
Organelle Targeting
GNPs are also capable of specifically targeting
malfunctioning organelles in tumor cells,
such as nuclei or mitochondria. The nucleus
is an important target in localized cancer
GOLD GOLD
NANOPARTICLES NANOPARTICLES
therapy since it controls the processes of
cell growth, proliferation, and apoptosis,
which are commonly defective in tumor
cells. Accumulation of GNPs inside nuclei
can disrupt faulty nuclear processes and
eventually induce cell apoptosis. The
structure of the GNP used to target the
nucleus determines the final effect. For
example, small spherical and “nanoflower”-
shaped GNPs compromise nuclear
functioning, but large GNPs do not. 10
Dysfunctional mitochondria are also valuable
“GNPS HAVE PRESENTED VIABLE MECHANISMS OF
ENTERING THE HUMAN BODY AND ALTERING TARGET
CELLS WHILE NOT INDUCING CYTOTOXIC RISKS.”
targets in localized therapy as they control
the energy supply of tumor cells and are
key regulators of their apoptotic pathways. 10
Specific organelle targeting causes internal
cell damage to cancerous tissue only, sparing
normal tissue from the damaging effects of
therapeutic agents. This makes nuclear and
mitochondrial targeting a desirable treatment
option that merits further investigation.
CHALLENGES OF GOLD NANOPARTICLES IN
LOCALIZED CANCER THERAPY
Cellular Uptake
Significant difficulties have been encountered
in engineering a viable method of cellular
GNP uptake. Notably, GNPs must not only
bind to a given cancer cell’s surface and
undergo endocytosis into the cell, but they
must also evade endosomes and lysosomes. 10
These obstacles are present regardless of
whether the GNPs are engineered to target
specific organelles or release therapeutic
agents inside cancerous cells. Recent
research has demonstrated that GNPs can
avoid digestion by being functionalized
with certain surface groups, such as
polyethylenimine, that allow them to escape
endosomes and lysosomes. 10
Toxic Effects on Local Tissue
The cytotoxic effects of GNPs on local cells
and tissues remain poorly understood. 11
However, recent research developments
have revealed a relationship between the
shapes and sizes of GNPs and their cell
toxicities. Larger GNPs have been found
to be more cytotoxic than smaller ones. 12
Gold nanospheres were lethal at lower
concentrations, while gold nanostars were
less toxic. 13 While different shapes and sizes
of GNPs can be beneficial in various localized
cancer therapies, GNPs must be optimized
on an application-by-application basis with
regard to their toxicity level.
CONCLUSION
Gold nanoparticles have emerged as viable
agents for cancer therapy. GNPs are effective
in targeting malignant cells specifically,
making them less toxic to normal cells than
traditional cancer therapies. By modifying
their surfaces with different chemical groups,
scientists can engineer GNPs to accumulate at
specific tumor sites. The shape and size of a
GNP also affect its behavior during targeting,
accumulation, and cellular endocytosis. After
accumulation, GNPs may be used to enhance
the efficacy of established cancer therapies
such as hyperthermia. Alternatively, GNPs
can deliver chemotherapy drugs to tumor
cells internally or target specific organelles
inside the cell, such as the nucleus and the
mitochondria.
Although some research has shown that
GNPs themselves do not produce acute
cytotoxicity in cells, other research has
indicated that nanoparticle concentration,
shape, and size may all affect cytotoxicity.
Therefore, nanoparticle design should be
optimized to increase cancerous cell death
but limit cytotoxicity in nearby normal cells.
MAGNETIC MAGNETIC
HYPERTHERMIA HYPERTHERMIA
THERAPY THERAPY
TUMOR
TUMOR
TUMOR
TUMOR
Sketch showing the injection
of gold nanoparticles into the
human body and their targeting
of and travel to the tumor site.
Hyperthermia therapy is then
applied to the tumor site using a
magnetic field.
CATALYST 26