Biomedical Engineering Reference
In-Depth Information
TABLE 17.3
Prominent Preclinical Magnetic Nanoparticle Heating Studies
Magnetic Core
Dimension
(nm)
Magnetic
Material
Animal
Model
Group
Ye a r
Particle Structure
Tumor Model
Successful Indications
Gilchrist et al.
1957
Nanoparticle
Maghemite
20-100
Dog
Lymph Node
Δ14°C after 3 minutes of
heating in lymph node.
Gordon et al.
1979
Dextran-Coated
Nanoparticle
Magnetite
< 6
Rat
Breast Carcinoma
Systemic injection with Δ8°C
and tumor necrosis.
Rand et al.
1981
Neede-Shaped
Microparticle
Ferromagnetic
100-1000
Rabbits
Renal Carcinoma
Tumor surface temp of 50°C
with complete cancer cell
necrosis.
Jordan et al.
1997, 2005
Coated Nanoparticle
Magnetite
3, 15
Mouse
Rat
Breast Carcinoma,
Malignant Glioma
Δ12°C resulted in 4.5 increase
in survival over control.
Hilger et al.
2002
Coated Nanoparticle
Magnetite
10, 200
Mouse
Breast Carcinoma
Δ12°C and Δ73°C with tumor
coagulation and necrosis.
Johannsen et al.
2005, 2006
Aminosilane-Coated
Nanoparticle
Magnetite
15
Rat
Prostate
Carcinoma
Combination, low-dose
radiotherapy with 88% tumor
regression.
Ohno et al.
2002
Stick-Type
Carboxymethyl-
cellulose
Magnetite
10
Rat
Glioma
Δ5°C with significant 30-day
increase in survival over
control.
Yanase et al.
1998, 1999
Magnetic Cationic
Liposome
(MCL)
Magnetite
10
Rat
Glioma
Δ6-8°C with tumor regression
in 90% of treated rats.
Le et al.
2001
Magnetic Cationic
Liposome
(MCL)
Magnetite
10
Mouse
Glioma
Anitbody targeting resulted in
60% retention of interstitial
injection.
Ito et al.
2003
Magnetic Cationic
Liposome
(MCL)
Magnetite
10
Mouse
Melanoma
Δ6-8°C with combined IL-2 or
GM-CSF results in complete
regression in 40 to 75% of
mice.
Tanaka et al.
2005
Magnetic Cationic
Liposome
(MCL)
Magnetite
10
Mouse, Rat
Melanoma
Combined dendritic cell
immunotherapy.
Kawai et al.
2005
Magnetic Cationic
Liposome
(MCL)
Magnetite
10
Rat
Prostate
Carcinoma
Δ7°C with demonstrated
tumor regression.
Motoyama et
al.
2008
Magnetic Cationic
Liposome
(MCL)
Magnetite
10
Rat
Breast Carcinoma
Δ7°C with tumor regression in
75% of the treated rats.
Natarajan et al.
2008
PEG-Coated
Nanoparticle
Iron Oxide
20, 30, 100
Mouse
Breast Carcinoma
Antibody targeting achieved
4-9% deposition of IV
injected dose.
Dennis et al.
2009
Dextran-Coated
Nanoparticle
Magnetite
44
Mouse
Breast Carcinoma
Up to 52°C with nearly
complete tumor regression at
highest dose.
A more detailed discussion of scaling between nano-, micro-, and
macroscale heating efects is included in Chapter 19, this topic.
An alternative explanation suggests that ferric ions produced by
the nanoparticles result in additional oxidative stress. In a sepa-
rate study, it was found that iron concentrations of 1 mM produce
no cytotoxic effects at 37°C, but became toxic at temperatures of
43°C (Freeman, Spitz, and Meredith 1990).
successful results spanning over five decades. A summary of
some of the most prominent studies is included in Table 17.3.
In addition to the successful indications, the exclusive use of
iron oxide (mainly magnetite) as the magnetic core material
should be noted. This again is due to the demonstrated ability
to produce heating and well-characterized biocompatibility.
Additional detail on several studies will follow.
Jordan et al. used intratumoral injection to administer super-
paramagnetic, dextran coated magnetite particles in intramuscu-
larly implanted mammary carcinoma of the mouse (Jordan et al.
1997). Upon ferrofluid injection, a bandage securing six magnets
was fixed on the tumor site. This static field gradient was intended
17.4.3 thermal Dose In Vivo
Encouraged by the promising results demonstrated in vitro a
number of groups have also pursued in vivo animal work, with
 
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