Biomedical Engineering Reference
In-Depth Information
membranes (Krpetie 2010) and mitochondria (Tong 2009), and
leads to apoptosis of the cell. The detailed mechanism of the ROS
generation with GNPs is not clear and requires further studies.
studies is listed in Table 18.7. One can see that the accumulation
of GNPs in the tumor is quite different between different studies.
After penetrating the leaky vessels, NPs will diffuse away from
the microvasculature. This process is size and charge dependent.
Larger NPs diffuse slower and tend to stay near the microvascu-
lature, while smaller NPs diffuse faster and distribute more uni-
formly throughout the tumor tissue over time (Perrault 2009).
The surface charge of NPs also affects the transport of NP in
the tissue. Positively charged NPs are more quickly internalized
in cancer cells, and negatively charged NPs diffuse deeper into
the tissue (Kim 2010). These fundamental studies can help the
engineering design of NPs for different purposes. For example,
small negatively charged NPs would be favorable for delivery of
attached drugs or contrast agents into deep tissue. The shape of
the NPs may also affect the transport within the tissue, but this
effect requires further study.
Comprehensive reviews on biodistribution (Khlebtsov 2010),
toxicity (Khlebtsov 2010, Fischer 2007), and immune response
of GNPs (Dobrovolskaia 2009, Dobrovolskaia 2007), are avail-
able for the interested reader. Once the GNP is delivered to the
tumor and the amount of GNP is sufficient for heating (based
on the scaling of Equation 18.14), the laser can be applied for
photothermal therapy as discussed next.
18.6.3
In Vivo
Effects
The use of GNP for photothermal therapy has been studied with
in vivo
tumor model systems (such as rodent and canine) and
is currently in a clinical trial (discussed in Section 18.7). This
section will focus on the issues of implementing GNP for pho-
tothermal therapy for tumors first by delivering the GNPs to the
tumor (i.e., biodistribution) followed by laser heating.
18.6.3.1 Overview of GNp Biodistribution
The successful intravenous delivery of NPs to the tumor
in vivo
relies on the enhanced permeability and retention (EPR) effects
due to the leaky vasculature in the tumor tissue. As the NPs are
circulating in the blood stream, they penetrate the leaky vessels
and accumulate in the tumor. Biodistribution studies show that
the reticuloendothelial system (RES) organs, such as liver and
spleen, take up the majority of the NPs injected (Perrault 2009,
Goel 2009). It is critical to increase the blood circulation time of
GNPs to enhance the NP delivery to the tumor. Some contro-
versy remains as to whether active delivery with tumor target-
ing ligands will increase the total NP accumulation in the tumor
(Nie 2010). The tumor uptake of GNPs for several representative
18.6.3.2 thermal Injury (Kinetics)
So far the thermal injury kinetics for
in vivo
laser GNP photo-
thermal therapy has not been carefully studied. Tissue responses
TABLE 18.7
Representative Studies on
In Vivo
Laser and Nanoparticle Doses for Cancer Photothermal Therapy and Scaling
of Temperature Change
NP Conc. at
Tu m o r
b
NP type
NP Info.
NP Dose
a
Laser Dose
ΔTscaling (K)
ΔTexp (K)
Ref.
110 nm Si
core/10 nm Au
shell, PEG
c
20~50 µL interstitial
injection, 1.5 × 10
10
NPs/ml
820 nm, 4 W/cm
2
,
5 mm
f
, <6 min
Au nanoshell
5-13 µg/g
d
20 ~ 50
28~60
(Hirsch 2003)
110 nm Si core/10
nm Au shell, PEG
100 µL, 2.4 × 10
11
NPs/ml
808 nm, 4 W/cm
2
,
5 mm, 3 min
NA
NA
20
g
(O'Neal 2004)
119 nm Si
core/12 nm Au
shell, PEG
150 µL, 1.5 × 10
11
NPs/ml
12.5 µg/g at
20 hr
808 nm, 4 W/cm
2
, 5
mm, 3 min
30
NA
(Gobin 2007)
40 µg/g at
24 hr
808 nm, 4 W/cm
2
,
5 mm, 3 min
75 µL, 7.7 × 10
11
NPs/ml
35/55 nm Au/Au
2
S
50
16~30
g
(Gobin 2010)
31 µg/g at
72 hr
e
810 nm, 2 W/cm
2
, 5
mm, 5 min
(von Maltzahn
2009)
Au nanorod
14 × 47 nm, PEG
20 mg Au/kg
20
40
6 ml/kg at 2.5 × 10
12
NPs/ml;
808 nm, 3.5 W, 3 min,
diffuse fiber 1 cm tip
-
14 × 45 nm, PEG
NA
30
(Goodrich 2010)
Note:
The information include the NP and its dose, the measured NP concentration at the tumor (if available), laser dose, temperature scaling, and reported
temperature change. Note that the temperature obtained through scaling is just a rough estimate of the magnitude of temperature increase.
a
The administration of NP is systemic unless otherwise noted.
b
The unit µg/g is similar to µg/mL as the tissue density is ~1g/mL.
c
PEG means that the particle is coated with polyethylene glycol (PEG)
d
Assumptions include the tumor volume of 0.5 cm
3
and uniform GNP distribution
e
Animal weight of 22 g was used (von Maltzahn 2009).
f
Laser beam size
g
The mouse skin temperature of 30°C is assumed.
