M. Angelakeris : Magnetic nanoparticles: A multifunctional vehicle for modern theranostics : 1 /30 May 8 th – 11 th , 2016, Varna-Bulgaria 6 th BIONANOMATERIALS PHYSICS AUTh - Greece Magnetic nanoparticles: A multifunctional vehicle for modern theranostics Particles Ensemble Conditions Add-ons Bio-practice M. Angelakeris, associate professor Department of Physics, Aristotle University 54124, Thessaloniki-Greece [email protected]http://multigr.physics.auth.gr
Transcript
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 1 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 2 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
Biomedical Applicability
Magnetic Hyperthermia
Cell Fate Control Drug Delivery
Bioseparation
BioSensing
MRI
Cell Capture
Cellular Proteomics
Cell Tracing
Types of Treatments
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 3 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
Contents
Particles
Ensemble
Conditions
Add-ons
Bio-practice
• biocompatibilty
• toxicity
• In-vivo efficiency
• Material Choice
• Size
• Shape
• Water Transfer
• Interactions
• Frequency
• Field intensity
• Magnetic Profile
• Drugs
• MRI
• Thermal Dose
What Particles?
Which Conditions?
Will it perform in bio?
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 4 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
Particles
Properties
Particles
Ensemble
Conditions
Add-ons
Bio-practice
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 5 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 6 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
Particles
Co
erc
ive
fie
ld
Su
pe
rpar
amag
ne
tism
ferromagnetism
monodomain multidomain
Particle Diameter (nm)
0
SM HM
SPM
0 20 100
Size ↓
↑ % surface atoms
Surface & Interface Magnetism
Size Issues
Particles
Ensemble
Conditions
Add-ons
Bio-practice
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 7 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
Particles
Ensemble
Conditions
Add-ons
Bio-practice
Particles
1st choice Tuning of magnetic anisotropy via shape anisotropy in magnetite particles
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 8 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
Particles
Ensemble
Conditions
Add-ons
Bio-practice
Particles
CoFe2O4
γ-Fe2O3
Fe3O4
FeCo
FePt
CoPt
Ni
Co
Alternatives
Metallic particles, spinel ferrites or special magnetic alloys
Other Choices 200 kJ/m3
Nanoparticle Diameter (nm)
0 20 40 60 80 100 120
4.7 kJ/m3
5 kJ/m3
412 kJ/m3
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 9 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
Nanomedicine: Nanotechnology, Biology, and Medicine
6 (2010) 362–370
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 1 0 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
Contents
Particles
Ensemble
Conditions
Add-ons
Bio-practice
• Material Choice
• Size
• Shape
• Water Transfer
• Interactions
What Particles?
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 1 1 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
Particles
Ensemble
Conditions
Add-ons
Bio-practice
Ensemble
Water Transfer
A versatile large-scale and green process for synthesizing magnetic nanoparticles with tunable magnetic hyperthermia features
accepted for publication in RSC Advances, 2016
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 1 2 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
Ensemble
single-core
core-shell arrays
50 nm
Interactions
Particles
Ensemble
Conditions
Add-ons
Bio-practice
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 1 3 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
Ensemble
Interactions
MFe2O4, M=Mn, Co
hard/softinterface
MFe2O4, M=Co, Mn or Fe
J. Magn. Magn. Mater. 81 179–187 (2015).J. Magn. Magn. Mater, accepted for publication, 2016
Tuning the magnetism of ferrite nanoparticles by nanoscale mixing and matching
Mn@Co
Co@Mn
Particles
Ensemble
Conditions
Add-ons
Bio-practice
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 1 4 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
Ensemble
Interactions
Particles
Ensemble
Conditions
Add-ons
Bio-practice
0 50 100 150 200 250 300
20
40
60
80
Theoretical
Experimental
Te
mp
era
ture
(oC
)
t (s)
Chain
Random
(a) (b)
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 1 5 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 1 6 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
Contents
Particles
Ensemble
Conditions
Add-ons
Bio-practice
• Material Choice
• Size
• Shape
• Concentration
• Colloidal Stability
• Interactions
• Frequency
• Field intensity
• Magnetic Profile
What Particles?
Which Conditions?
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 1 7 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
ConditionsParticles
Ensemble
Conditions
Add-ons
Bio-practice
Out of plane component of ac susceptibility: χ’’=χοωτ/(1+(ωτ)2)
FM particles: dependence of hysteresis losses on frequency is linear
SPM particles: non-linear frequency dependence of the imaginary part of the susceptibility
0 200 400 600 800 10000
20
40
60
80
100
nanomag-D 100 nm
SA
R (
W/g
)
Frequency (kHz)
M. Kallumadil et al. JMMM 321 1509 (2009).
SLP
(W
/g)
765
kHz
75 W/g
R. Hergt et al. J. Phys.: Condens. Matter 18 S2919-S2934 (2006).
PSPM = μ0πf χ’’H2~39 H2
Ø 11 nm
765
kHz
13
Frequency
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 1 8 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
ConditionsParticles
Ensemble
Conditions
Add-ons
Bio-practice
Atkinson et al developed a treatmentsystem based on eddy current heating ofimplantable metal thermoseeds.
W. Atkinson et al. IEEE Trans. Biomed. Eng. BME 31 70-5 (1984). I. A. Brezovich, Med. Phys. Monograph 16 82–111 (1988).
According to the induction law the induced heating power is proportional to (H · f · D)2
Brezovich found for a loop diameter of ~ 30 cm that a ‘test person has a sensation of warmth, but withstand s
the treatment for more than one hour without major discomfort
smaller diameter of the body region, smaller time scale
Exposure to fields where the product H · f < 4.85 Χ 108Am−1 s−1 is safe and tolerable
First commercially developed equipment (Gneveckow et al 2004) : 1.8 Χ 109 Am−1 s−1
Amplitude
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 1 9 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
ConditionsParticles
Ensemble
Conditions
Add-ons
Bio-practice
Particle type dependent magnetic losses: SPM particles ~ H2, FM particles ~ H3
Magnetic Profile
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/-
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 2 0 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
Contents
Particles
Ensemble
Conditions
Add-ons
Bio-practice
• Material Choice
• Size
• Shape
• Water transfer
• Interactions
• Magnetic Profile
• Frequency
• Field intensity
• Drugs
• MRI
• Thermal Dose
What Particles?
Which Conditions?
Will it perform in bio?
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 2 1 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
Add-0ns
Heat triggersCargo can be released in response to
Magnetic-hyperthermia triggered drug release system
external stimuli:light or a magnetic field
internal stimuli:natural biochemistry
inside cells using redox, enzymes, or a pH change in the cellular
compartments
RSC Adv. 3, 24367 (2013).
Particles
Ensemble
Conditions
Add-ons
Bio-practice
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 2 2 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
Commercial Ferrofluids
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).
Add-0nsParticles
Ensemble
Conditions
Add-ons
Bio-practice
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 2 3 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
In-vitro testing
MnFe₂O₄ nanoparticles
moderate magnetic moment,
chemical stability and
high specific loss power (SLP)
Successful in-vitro hyperthermia in Saos-2
J. Mater. Chem. B 2, 8390 (2014).
Add-0nsParticles
Ensemble
Conditions
Add-ons
Bio-practice
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 2 4 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
In-vitro testing
SaOS-2 (top), C2-C12 (middle), 3T3-L1 (bottom).
More effective agentsNew Protocols with lower thermal doses
Add-0nsParticles
Ensemble
Conditions
Add-ons
Bio-practice
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 2 5 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
Contents
Particles
Ensemble
Conditions
Add-ons
Bio-practice
• biocompatibilty
• toxicity
• In-vivo efficiency
• Material Choice
• Size
• Shape
• Concentration
• Colloidal Stability
• Interactions
• Magnetic Profile
• Frequency
• Field intensity
• Drugs
• MRI
• Thermal Dose
What Particles?
Which Conditions?
Will it perform in bio?
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 2 6 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
Bio-practiceMNPs due to their multivalency and multifunctionality, pose challenge for understanding their
pharmacokinetics because different components will have different features that affect their
toxicity, distribution, clearance and catabolism.
Dose
Concentration
Dosology
Dimensions
Size
Surface Area
Aspect Ratio
Durability
Chemictry
Crystal Structure
Surface Cover
Functionalization
Particles
Ensemble
Conditions
Add-ons
Bio-practice
Constraints
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 2 7 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
In-vitro testing
Particles
Ensemble
Conditions
Add-ons
Bio-practice
Bio-practice
Dose-dependent proliferation assay on 3T3 cells bymonitoring the 24-hour cell growth. Normalproliferation rates were obtained at all concentrationstested.
T2-weigthed MR images of mouse body before (left) and after injection of NPs.Because of the negative contrast properties of the solution, the liver appearshypointense in images after contrast injection (see arrow). (B) Color-coded T2maps, from yellow (high T2) to green (low T2). (C) Comparison of magnetic signalfrom targeted liver at the same time points as imaged by MRI. Maximumconcentrations (~ 90% of the injected dose) were observed 24 hours after injection.
Nanomedicine: Nanotechnology, Biology, and Medicine 6 (2010) 362–370
Fe/MgO nanoparticles
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 2 8 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
In-vitro testing
Cell fate control with magnetic field dancing modes
Magnetic nanoparticles may also be used to generate mechanical stimulations on cells
which can induce changes in cell activity such as differentiation, growth and death.
1 10
50
60
70
80
90
100 200mT
50mT
100mT
60mT
40mT
Force/MNP100nm
(pN)
Ce
ll V
iab
ility
(%
)
Force/Cell (pN)
1E-4 1E-3
Bio-practiceParticles
Ensemble
Conditions
Add-ons
Bio-practice
Nano-screenMAG-D, Chemicell GmbH on HT.29 cells (human colorectal adenocarcinoma)
Blue : cell nucleusRed : Lysosomes
Hetero-nanocomposites: 30 nm Cu2O nanoparticles with antifungal properties
functionalized with 9 nm NiFe2O4 magnetic nanoparticles as a platform for
magnetomechanical stress in Saccharomyces cerevisiae: J. Mater. Chem. B, 2015, 3, 5341
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 2 9 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
Magnetic nanoparticles:
A multifunctional vehicle for modern theranostics
Conclusions1G: Magnetics
• To design, control and measure magnetic response at the nanoparticle unity.
2G: Nano
• To achieve and reproduce nanoscale multicomponent fabrication.
3G: Bio
• To introduce multifunctionality without sparing enhanced performance.
4G: Medical
• To increase biocompatibilty and sustain enhanced mulifunctionality in-vivo.
M . A n g e l a k e r i s : M a g n e t i c n a n o p a r t i c l e s : A m u l t i f u n c t i o n a l v e h i c l e f o r m o d e r n t h e r a n o s t i c s : 3 0 / 3 0May 8th – 11th, 2016, Varna-Bulgaria
6th B I O N A N O M A T E R I A L S P H Y S I C SA U T h - G r e e c e
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, Greece
![017-652 001 teliko SOSTO - users.auth.grusers.auth.gr/adagkas/texts/3. 017-652_001.pdf · Το κοµµατικό αρχείο. ∆ιαδροµές, εµπλοκές [21] αφήγησης,](https://static.documents.pub/doc/80x56/5dd1094dd6be591ccb63e903/017-652-001-teliko-sosto-usersauth-017-652001pdf-oe.jpg)
![On the syntax and semantics of verb ... - users.auth.grusers.auth.gr/sioupi/LA 45 Sioupi.pdf · semantic analysis. Since Greek is a NP[–arg, +pred] language, as it is pro-posed,](https://static.documents.pub/doc/80x56/5f0c04cc7e708231d4335a2d/on-the-syntax-and-semantics-of-verb-usersauth-45-sioupipdf-semantic-analysis.jpg)
