magnetic hyperthermiausers.auth.gr/agelaker/index_htm_files/angelakeris3-pam3...hyperthermia differs...
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 1 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Magnetic Hyperthermia:
A versatile platform for heat-triggered modalities
Principle
Parameters
Conditions
Functions
M. Angelakeris, associate professorDepartment of Physics, Aristotle University
54124, Thessaloniki-Greece
http://multigr.physics.auth.gr
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 2 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Introduction-Heat treatmentsPrinciple
Parameters
Conditions
Functions
1891: A century ago, Dr. William Coley an innovative New York surgeon induced
a fever in the body of a cancer patient to stimulate the immune response and
cause cancer remission.
Coley’s toxins: Bacteria used to treat patients with a variety of types of cancer
up until the early 1950s. More than 1,000 patients over 40 years.
“What medicine cannot cure,
iron (the knife) cures;
what iron cannot cure, fire cures ;
what fire does not cure, is to be considered incurable”
Hyperthermia is elevated body temperature due to failed thermoregulation that occurs when
a body produces or absorbs more heat than it dissipates.
Hyperthermia differs from fever in that the body's temperature set point remains unchanged.
500 BC: Hippocrates
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 3 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Introduction-Hyperthermia typesPrinciple
Parameters
Conditions
Functions
Hyperthermia: Treatments at temperatures of 41–45 ◦C
for up to few hours—actually denoted as
hyperthermia—need a combination with other assisting
toxic agents (mostly irradiation or chemotherapy) for
reliable damage of tumor cells.
Local hyperthermia: the local temperature increase with respect to standard temperature of the human
body is considered to be therapeutically useful over a relatively broad temperature range where different
mechanisms of cell damaging occur with increasing temperature.
Local intracorporal heat generation by: microwave radiation, capacitive or inductive coupling of
radiofrequency fields, implanted electrodes, ultrasound, lasers.
Thermoablation: aims for the thermal killing
of all tumor cells by applying temperatures
in excess of at least 50 ◦C in the tumor
region for exposure times of at least few
minutes.
Whole body hyperthermia: the
systemic temperature has to be
carefully controlled to ~41.8 ◦C
by a heat bath.
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 4 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Magnetic HyperthermiaPrinciple
Parameters
Conditions
Functions
Magnetism + hyperthermia:
1957: Gilchrist and others proposed the use of magnetic materials in
hyperthermia.
Today: MPH: Magnetic Particle Hyperthermia: The use of magnetic
nanoparticles improves hyperthermia cancer treatment.
Hyperthermia vs cancer:
Many tumors thrive in a hypoxic environment in which the
oxygenation of the tumor is much lower than in normal tissue.
Because tumors cannot dissipate heat as quickly as healthy tissue, they
can get hotter than that tissue if enough heat is applied.
Hyperthermia at relatively low levels — as in the early clinical use of
thermal medicine — ends up increasing the amount of blood flow and
oxygenation of the tumor, making it more sensitive to radiation and
chemotherapies.
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 5 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Principle
Parameters
Conditions
Functions
Field Frequency: 100-1000 kHz
Field Amplitude: 10-100 kA/m
Magnetic Hyperthermia-Setup
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 6 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Magnetic hyperthermia-MechanismsPrinciple
Parameters
Conditions
Functions
Γ=KV/kBT
A=αμοMSHC
Co
erc
ive
fie
ld
Su
pe
rpar
amag
ne
tism
ferromagnetism
monodomain multidomain
Particle Diameter
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 7 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Principle
Parameters
Conditions
FunctionsMagnetic hyperthermia-Parameters
Magnetic losses
Hysteresis losses
~2 K
Néel relaxation
τΝ=τ0eKV/kT
Brown relaxation
τΒ=4πnrh3/kT
Viscous losses
~2πμ0ΜRHV
Induced Heating Power
~ H2 f2 D2
Effective relaxation
τeff=τΝτΒ/(τΝ+τΒ)
Ferromagneticparticles
Superparamagneticparticles
Magnetic losses
to be utilized for heating
different processes of
magnetization reversal
different manners on
the applied magnetic AC: field amplitude and frequency.
the structure: mean size, width of size distribution, particle
shape and crystallinity.
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 8 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Magnetic hyperthermia-ProcessPrinciple
Parameters
Conditions
Functions
Obtained data corrected for heat losses
Coil heating effect
Environmental losses
ΔΤ/Δt
Τ=Το+be-Kt
Specific Loss Power
(SLP) calculation
J. Magn. Magn. Mater. 323 775-780 (2011).J. Appl. Phys. 114, 103904 (2013).
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 9 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Principle
Parameters
Conditions
FunctionsMagnetic hyperthermia-Parameters
Size: 10 < D < 30 nm
Saturation Magnetization: 60 < Ms < 100 A m2/kg
Anisotropy: 5 < Keff < 40 KJ/m3
heat⇔SLPmax
Material
DosageConditions
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 1 0 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Principle
Parameters
Conditions
FunctionsTypes of materials-Sizes
28
SLP
(W/g
Fe) SPM
maximum
FM maximum
22 KA/m
Fe3O4: IEEE Trans. on Magn. 48 1320,( 2011).MnFe2O4: Dalton Trans. 44 5396 (2015).
further increase of particle size:
MonodomainMultidomain
coercivity & remanence decrease
decrease of hysteresis losses
Iron oxide particles
below ~ 20 nm become
superparamagnetic
a maximum of hysteresis losses
may be expected
for single domain iron oxide particles
near ~ 30 nm
PSPM = μ0πf χ’’H2
HdMf0 FMP
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 1 1 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Principle
Parameters
Conditions
FunctionsTypes of materials-Sizes
R. Hergt et al. J. Phys.: Condens. Matter 20 385214 (12pp) (2008).
Narrow size distribution (w=0.7 nm)
Broad size distribution (w=7 nm)
Reduction of field amplitude below saturation
decrease of heat output.
The amount of decrease depends specifically on the
mean size and the distribution width.
Broad size distribution not very sensitive to changes
of mean size.
Narrow size distribution depression of losses for
medium sizes.
The maximum loss may be gained only if Ho > Hc is above
the coercivity of the majority of particles.
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 1 2 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Principle
Parameters
Conditions
FunctionsTypes of materials-Shapes
Tuning of magnetic anisotropy via shape anisotropy in magnetite particles
Scientific Reports | 3 : 1652 | DOI: 10.1038/srep01652 (2013).
-1.0 -0.5 0.0 0.5 1.0
-100
-50
0
50
100
20 nm spheres
20 nm squares
40 nm squares
Ma
gn
eti
za
tio
n (
Am
2/k
g)
Magnetic field (T)
300 K
50 nm
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 1 3 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Principle
Parameters
Conditions
FunctionsTypes of materials-Combinations
single-core
core-shell arrays
50 nm
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 1 4 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Principle
Parameters
Conditions
FunctionsTypes of materials-Combinations
Metallic Fe
hard/softinterface
Fe3O4 or γ-Fe2O3
Tuning the magnetism of ferrite nanoparticles
Sample Target (%wt) Chamber’s
pressure/Gas
Composition (%wt) XRD/Mossbauer analysis Average Size
(nm)
Morphology*
Fe Fe3O4 Fe FeO Fe3O4 γ-
Fe2O3 Core/Shell(s)
(nm) Scheme
F01 100 - 70 torr/Ar 79.4
77.7 -
20.6
22.3 50 44/3
F02 75 25 70 torr/Ar 58.6
69.8
10.1
5.2
31.3
25.0 52 42/2/3
F03 75 25 50 torr/Ar 53.6
67.5
11.8
13.1
34.6
-
-
19.3 33 25/1/3
F04 50 50 70 torr/Ar 12.9
11.1
14.7
8.4
72.4
80.6 48 24/4/8
F05 - 100 80 torr/Ar 9.1
5.9 -
90.9
94.1 78 30/24
F06 - 100 80 torr/Ar-O2 - -
4.6
-
58.0
100
37.4 43 43/-
Sample Target (%wt) Chamber’s
pressure/Gas
Composition (%wt) XRD/Mossbauer analysis Average Size
(nm)
Morphology*
Fe Fe3O4 Fe FeO Fe3O4 γ-
Fe2O3 Core/Shell(s)
(nm) Scheme
F01 100 - 70 torr/Ar 79.4
77.7 -
20.6
22.3 50 44/3
F02 75 25 70 torr/Ar 58.6
69.8
10.1
5.2
31.3
25.0 52 42/2/3
F03 75 25 50 torr/Ar 53.6
67.5
11.8
13.1
34.6
-
-
19.3 33 25/1/3
F04 50 50 70 torr/Ar 12.9
11.1
14.7
8.4
72.4
80.6 48 24/4/8
F05 - 100 80 torr/Ar 9.1
5.9 -
90.9
94.1 78 30/24
F06 - 100 80 torr/Ar-O2 - -
4.6
-
58.0
100
37.4 43 43/-
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 1 5 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Principle
Parameters
Conditions
FunctionsTypes of materials-Combinations
MFe2O4, M=Mn, Co
hard/softinterface
MFe2O4, M=Co, Mn or Fe
J. Magn. Magn. Mater. 81 179 (2015)J. Mag. Magn. Mater. 415, 20 (2016)RSC Adv., 6, 53107 (2016)RSC Adv. 6, 72918 (2016)
Tuning the magnetism of ferrite nanoparticles
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 1 6 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Principle
Parameters
Conditions
FunctionsTypes of materials-Combinations
Tuning the magnetism of ferrite nanoparticles
Cluster size dependent magnetic losses
50 nm
100 nm
40 50 60 70 80 90 100100
200
300
400 SLP
SL
P (
W/g
)
Size (nm)
H=25kA/m -f=765kHz
100
200
300
400
H.L.
Hyste
resis
Lo
sse
s (W
/g)
50 nm
Mat. Sci. Eng. C 58, 187–193 (2016)
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 1 7 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Principle
Parameters
Conditions
FunctionsTypes of materials-Combinations
Tuning the magnetism of ferrite nanoparticles
Scientific Reports, Nature, accepted for publication, 2016
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 1 8 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Conditions-Field effectPrinciple
Parameters
Conditions
Functions
Out of plane component of ac susceptibility: χ’’=χοωτ/(1+(ωτ)2)
experimental time constant: ω-1=(2πf)-1
ω-1=τ: determination of TBω-1>τ : thermal relaxation takes place
ω-1
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 1 9 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Conditions-Field effectPrinciple
Parameters
Conditions
Functions
H
(kA m-1)
f
(kHz)
Hf
(109A m-1 s-1)Reference
18 100 1.8 1
10 410 4.1 2
32 183 5.9 3
19 435 8.3 4
37.3 500 18.7 5
A restriction limits the range of frequency that can be
employed, considering the safety and patient tolerance
limits below which the eddy current effects are
affordable.
Originally, a maximum field - frequency product
Hf ≤ 4.85 × 108 A m-1s-1 called the Atkinson-Brezovich
limit was proposed in 1984, based on micron-sized
magnetic implants.
However, up to date practice, has shown that such a
limitation is rather stringent and should be reconsidered
by including both the nanoscale character of the particles
and the treatment itself.
1. B. Thiesen & A. Jordan (1st clinical magnetic hyperthermia
application) Int. J. Hyperthermia, September 2008; 24(6): 467–474
2. R. Hergt et al. J. Magn. Magn. Mater. 2005, 293, 80–86.
3. E. Alphandéry et al. ACS Nano 2011, 5 (8), 6279–6296.
4. S. Kossatz et al. Pharm Res (2014) 31:3274–3288
5. H. Mamiya, Journal of Nanomaterials 2013, Article ID 752973
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 2 0 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Conditions-Concentration effectPrinciple
Parameters
Conditions
Functions
140 160 180 200 220 240 260 2800
100
200
300
400
500
600
Ø18 nm
c/7
c
Ø10 nm
c/7
c
SA
R (
W/g
Fe)
H (Oe)
Iron Oxide MNPs
c=1.2 mg/ml
ΔSAR=255
ΔSAR=328
SLP
ΔSLP
ΔSLP
SLP decreases with increasing concentration
Static susceptibility decrease
Néel relaxation time decrease
faster τ dominates
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 2 1 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Conditions-Concentration effectPrinciple
Parameters
Conditions
Functions
J. Appl. Phys. 108, 073918 (2010).
Adv. Funct. Mater. DOI: 10.1002/adfm.201200307, 2012.
Sci.Rep. 2016, Accepted for publication
Single-domain metallic Fe MNPs
Effective uniaxial magnetic anisotropy Keff
Uniform magnetization and composition
decrease in the initial susceptibility with increasing c, so that the
stronger the interaction between particles, the lower the SLP.
SLP saturates to a constant value for large fields
the saturation taking place at larger values for larger concentrations.
Ha (larger the higher the concentration) gives the upper limit for the
field amplitude for larger SLP.
Ha=2 K/MSanisotropy field
SLP
/f (
J/k
g)
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 2 2 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Conditions-Field effectPrinciple
Parameters
Conditions
Functions
In-vitro Hyperthermia
Versatile in-vitro hyperthermia protocol
(two hyperthermia runs separated by a
48 h incubation stage).
Single-pulse or a multi-pulse AC field
exposure with tunable time duration in
order to maintain the cells as long as
possible between 41 and 45oC, i.e. the
hyperthermia region.
Check in-vitro performance in human
osteosarcoma cell line (SaOs-2) and in two
reference healthy cell lines (C2C12 skeletal
myoblasts and 3T3-L1 fibroblast-like
preadipocytes).
(a) (b) (c)
0 200 400 600
41
43
45
Te
mpe
ratu
re (
oC
)
Time (sec)
Co+Fe
Mn+Fe
(b)
0 200 400 600 800 1000
34
36
38
40
42
44
46
hyp
ert
he
rmia
leve
ls 4
1-4
5oC
Control
Mn+Fe
Co+Fe
Te
mp
era
ture
(oC
)
Time (sec)
Mn+Fe Co+Fe Control(a)
0 200 400 600 800 1000
34
36
38
40
42
44
46 Mn+Fe Co+Fe Control
Control
Tem
pera
ture
(oC
)
Time (sec)
Co+Fe
Mn+Fe
hyp
ert
he
rmia
leve
ls 4
1-4
5oC
(e)
0 200 400 600
41
43
45
Mn+Fe
Co+Fe
Te
mp
era
ture
(oC
)
Time (sec)
(f)
Saos-2 sample Prusian Blue stained
(a) control sample
(b) with Mn+Fe MNPs
(c) With Co+Fe MNPS
Int J Hyperthermia 2016, 32(7):778-85.
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 2 3 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Functions-Tuning hyperthermia responsePrinciple
Parameters
Conditions
Functions
K. L. McNerny et al. J. Appl. Phys. 107 09A312 (2010).
Fe27Pt73, Ni28Pd72, TC~45oC
Ni alloys: Ni-Cu, Ni-Pd, Ni-Pt
Fe-Pt alloys, Co-Pd alloys
Ferrites: Fe1-xMnxFe2O4
Magnetic nanoparticles possessing low Curie temperatures
(TC) offer the possibility for self regulated heating of cancer
cells, where the TC acts as an upper limit to heating to
prevent damage to neighboring healthy tissues.
Once they reach the Curie temperature, the Ms drops to zero
and heating stops.
Thus if the Curie temperature is fixed by judicious selection of
particle composition and size hyperthermia response is
eventually fixed below a certain temperature level preventing
excessive temperatures.
Self-regulated hyperthermia
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 2 4 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Principle
Parameters
Conditions
Functions
To investigate the usefulness of a method for controlling the
temperature rise in magnetic hyperthermia (MH) using an external
magnetic field to manipulate the energy dissipation of magnetic
nanoparticles in the presence of both fields
Functions-Tuning hyperthermia response
High-Performance Iron Oxide Nanoparticles forMagnetic Particle Imaging – Guided Hyperthermia(hMPI)
Appl. Field (f=380kHz, Ho=16kA/m)
To mimic the magnetic environment during an MPI imaging Process -
external magnetic field gradient (0.47T/m gradient across the
hyperthermia coil with a null point near the center
L. M. Bauer et al. Nanoscale, 2016,8, 12162-12169
Control of the temperature rise in magnetichyperthermia with use of an external static magneticfield K. Murase et al. Phys Med. 2013;29(6):624-30
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 2 5 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Functions-NanoplatformsPrinciple
Parameters
Conditions
Functions
A. Ito et al. Cancer Immuniol. Immunother. 55 320-328 (2006).
Interaction with the Immune System
Hyperthermia based controlled drug-delivery
Hyperthermia & Diagnosis
Μultifunctional NPs with a γ-Fe2O3 core and
labeled with a targeting agent LHRH
(Luteinizing Hormone Release Hormone)
ensured specific targeting to cancer cells of
breast and prostate in addition to having a
two-photon fluorescent probe to aid in
optical tracking.
Delivery through Bond Breaking (DBB)
Delivery through Enhanced Permeability (DEP)
C. S. S. R Kumar et al. Advanced Drug Delivery Reviews 63 789-808 (2011)
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 2 6 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Principle
Parameters
Conditions
Functions
Magnetic-hyperthermia triggered drug release system
RSC Adv. 3, 24367 (2013).
Functions-Nanoplatforms
Highly faceted IOs
Encapsulation in biodegradable block copolymers
Hyperthermia & Taxol drug release
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 2 7 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Principle
Parameters
Conditions
Functions
The major advantage of such a study is that an optimum system
directly addresses the multifunctional role in modern
theranostics and may be further implemented in therapies with
faster steps since major tasks have already been undertaken.
A series of commercially available magnetic iron oxide nanoparticles (Nanomag®-D-spio,
FeraSpin R and FluidMag-DX) as multifunctional biomedical carriers combining their initial
modality (i.e. MRI contract agents or drug carriers) with heat triggered actions.
J. Magn. Magn. Mater. 380 360-364 (2015).
EPJ Web of Conferences 75, 08002 (2014).
Functions-Nanoplatforms
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 2 8 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Functions-Multimodal Cancer RegimensPrinciple
Parameters
Conditions
Functions
Radiation sensitizers
Chemo-therapeutic
cocktails
Surgery
Targeted therapeutic
agents
Platinum therapeutics
Multimodal
Regimens
• Radiation and chemotherapy induce
DNA damagedouble strand breaks oxygen radicals
• Hyperthermia increases
• oxygenation levels in cancer cells
• Hinders the ability of cancer cells to sense DNA
destruction
• Impedes DNA repair mediators
Hyperthermia synergizes with
Radiation therapy
Chemotherapy: (arsenic trioxide, tirapazamine, cisplatin)
+ hyperthermia
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 2 9 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Magnetic hyperthermia-Questions Principle
Parameters
Conditions
Functions
In vivo studies
Cell: 10-100 μm,
Virus: 20-450 nm
Gene: 2nm wide, 10-100 nm long
Hydrodynamic parameters
Blood flow rate
Ferrofluid concentration
Infusion route
Circulation time
Psysiological parameters
Tissue depth & perfusion
Tumour volume
Strength of carrier/binding in varying enrnoment
Side-effects of high frequency magnetic fields
Stimulation of peripheral or skeletal muscles
Possible cardiac stimulation and arrythmia
Non-specific inductive heating of tissue
Circulation & Accumulation
Circumvention of rapid kidney clearance and reticular endothelial system (RES)
Design to avoid rapid opsonization and subsequent macrophage phagocytosis
Slow accumulation through the leaky vasculature in a variety of lesions
Metallic Iron upon metabolism – oxidative stress through harmful reactive oxygen species
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M . A n g e l a k e r i s : M a g n e t i c H y p e r t h e r m i a : A v e r s a t i l e p l a t f o r m f o r h e a t - t r i g g e r e d m o d a l i t i e s 3 0 / 3 0P H Y S I C SA U T h - G r e e c ePAMS-3
3rd PAM International School on Application of Nanomaterials in Medicine, 2-4 November, 2016, Tehran, Iran
Colleagues
M. Farle & group members, Germany
Ll. Balcels, C. Boubeta, D. Serantes, Spain
K. Chliclia, K. Spriridopoulou, M. Tziomaki, M. Yavropoulou, Greece
K. Dendrinou-Samara, O. Kalogirou, T. Samaras, AUTh-Greece
Group members
K. Simeonidis, Dr.
D. Sakellari, Dr.
A. Makridis, PhD student
E. Mirovali, PhD student
N. Maniotis, PhD student
Acknowledgements