nanomagnetism & biomedical applicability
TRANSCRIPT
M . A n g e l a k e r i s : N a n o m a g n e t i s m a n d B i o m e d i c a l A p p l i c a b i l i t y 1 / 2 3P h y s i c sA U T h
Workshop: Materials at the Nanoscale, 3-4 November, 2018, Thessaloniki-Greece
Hellenic Society for the Science and Technology of Condensed Matter
Nanomagnetism &
Biomedical applicability
M. Angelakeris, Associate Professor
Magnetic Nanostructure Characterization Group:
Technology & Applications
Department of Physics, Aristotle University of Thessaloniki,
54124 Thessaloniki, Greece
http://magnacharta.physics.auth.gr
email: [email protected]
M . A n g e l a k e r i s : N a n o m a g n e t i s m a n d B i o m e d i c a l A p p l i c a b i l i t y 2 / 2 3P h y s i c sA U T h
Workshop: Materials at the Nanoscale, 3-4 November, 2018, Thessaloniki-Greece
Hellenic Society for the Science and Technology of Condensed Matter
Magnetism around us
Though some are plainly
visible, others are often
tucked inside the inner
workings of appliances
and other household,
medical and commercial
items, doing their job
silently and unseen.
▪ You come into contact with magnets many times in the
course of your daily life.
▪ They play an important role in a wide range of devices
including simple toys, computers, credit cards, MRI
machines and business equipment.
▪ Magnets range in size from barely-visible specks to
industrial monsters weighing tons.
M . A n g e l a k e r i s : N a n o m a g n e t i s m a n d B i o m e d i c a l A p p l i c a b i l i t y 3 / 2 3P h y s i c sA U T h
Workshop: Materials at the Nanoscale, 3-4 November, 2018, Thessaloniki-Greece
Hellenic Society for the Science and Technology of Condensed Matter
The origin of Magnetism
Since electric current is the guided motion of electrons, electrons orbiting around a nucleus or spinning
around themselves are actually electric currents producing magnetic fields.
Each electron holds an orbital magnetic moment (rotation)
and a spin magnetic moment (spinning). Each electron is thus a tiny magnet.
Adding these microscopic magnetic moments for an atom, molecule,
crystal, body results to a macroscopic magnetization value.
In a typical electromagnet, the magnetic field is originated due to the electric current flowing in a
conductor.
What happens in a typical bar magnet?
M . A n g e l a k e r i s : N a n o m a g n e t i s m a n d B i o m e d i c a l A p p l i c a b i l i t y 4 / 2 3P h y s i c sA U T h
Workshop: Materials at the Nanoscale, 3-4 November, 2018, Thessaloniki-Greece
Hellenic Society for the Science and Technology of Condensed Matter
Magnetism & Periodic Table
Antiferromagnetism Diamagnetism Ferromagnetism Paramagnetism
Elements of the periodic table are
split in 4 major categories with
respct to the value of their
magnetic susceptibility
Most materials of the
periodic tables are
diamagnetic and
paramagnetic materials at
room temperature.
In most of materials, the
total magnetic moment, is
zero due the organization of
electrons in couples.
M . A n g e l a k e r i s : N a n o m a g n e t i s m a n d B i o m e d i c a l A p p l i c a b i l i t y 5 / 2 3P h y s i c sA U T h
Workshop: Materials at the Nanoscale, 3-4 November, 2018, Thessaloniki-Greece
Hellenic Society for the Science and Technology of Condensed Matter
Types of Magnetism𝜒 =
Μ
Ηχ=0
Diamagnetism: χ<0
Paramagnetism: χ>0
Ferromagnetism: χ>>0
Superconductivity
Ferrimagnetism
Antiferromagnetism
Magnetic
Order
Magnetic
Disorder
M . A n g e l a k e r i s : N a n o m a g n e t i s m a n d B i o m e d i c a l A p p l i c a b i l i t y 6 / 2 3P h y s i c sA U T h
Workshop: Materials at the Nanoscale, 3-4 November, 2018, Thessaloniki-Greece
Hellenic Society for the Science and Technology of Condensed Matter
2D: magnetic arrays
3D: magnetic nanoparticles1D: magnetic multilayers
Nanomagnetic Materials
0 20 40 60 80 100
Co
Fe
Ni
Mn-ferrite
Co-ferrite
Ni-ferrite
Magnetite
Maghemite
CoPt
FePt
FeCo
10
20
30
4.3
10
20
25
35
3
4
16
Nanoparticle Diameter (nm)
3 kJ/m3, 110 A m2/kg
6.2 kJ/m3, 47 A m2/kg
Alloys
Ferrites
Elements
9 kJ/m3, 89 A m2/kg
4.7 kJ/m3, 85 A m2/kg
4000 kJ/m3, 46 A m2/kg
7000 kJ/m3, 75 A m2/kg
1.5 kJ/m3, 201 A m2/kg
200 kJ/m3, 85 A m2/kg
5 kJ/m3, 59 A m2/kg
412 kJ/m3, 163 A m2/kg
48 kJ/m3, 222 A m2/kg
SPM ⇒ SD SD ⇒MD
M . A n g e l a k e r i s : N a n o m a g n e t i s m a n d B i o m e d i c a l A p p l i c a b i l i t y 8 / 2 3P h y s i c sA U T h
Workshop: Materials at the Nanoscale, 3-4 November, 2018, Thessaloniki-Greece
Hellenic Society for the Science and Technology of Condensed Matter
Ferrofluids
A ferrofluid (a composite word from
ferromagnetism and fluid) is a fluid magnetized
strongly in the presence of magnetic field.
Ferrous materials are colloidal fluids made of magnetic
micro- or nano- particles suspended in a fluid carrier
(usually an organic solvent or water).
M . A n g e l a k e r i s : N a n o m a g n e t i s m a n d B i o m e d i c a l A p p l i c a b i l i t y 9 / 2 3P h y s i c sA U T h
Workshop: Materials at the Nanoscale, 3-4 November, 2018, Thessaloniki-Greece
Hellenic Society for the Science and Technology of Condensed Matter
https://www.youtube.com/watch?v=uva1fixU_zg
https://www.youtube.com/watch?v=6Kzrwq2WJkY
Nanoparticle Synthesis
Magnetic nanoparticles
Magnetic nanoparticle suspensions
10
1. Alternative: with the possibility to obtain stable
colloids using MNPs, they can be administered
through a number of drug delivery routes.
2. Selective: MNPs can be targeted through
specific binding agents making the treatment
much more selective and effective.
3. Cancer-specific: cancer cells absorb MNPs
thereby increasing the effectiveness of
treatment.
4. Brain tumors: MNPs can also effectively cross
blood-brain barrier (BBB) and hence can be used
for treating brain tumors.
5. Homogenous: compared to macroscopic
implants, MNPs provide much more efficient
and homogeneous treatment.
M . A n g e l a k e r i s : N a n o m a g n e t i s m a n d B i o m e d i c a l A p p l i c a b i l i t y 1 1 / 2 3P h y s i c sA U T h
Workshop: Materials at the Nanoscale, 3-4 November, 2018, Thessaloniki-Greece
Hellenic Society for the Science and Technology of Condensed Matter
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 : N a n o m a g n e t i s m a n d B i o m e d i c a l A p p l i c a b i l i t y 1 2 / 2 3P h y s i c sA U T h
Workshop: Materials at the Nanoscale, 3-4 November, 2018, Thessaloniki-Greece
Hellenic Society for the Science and Technology of Condensed Matter
Nanotheranostics
Theranostics arises from the combination of the terms "Therapeutics" and "Diagnostics" and is
used to describe a proposed process of diagnostic therapy for individual patients - to test them
for possible reactions when taking a new medication and to tailor a treatment for them based on
personalized test results. The prefix Nano means that nanomaterials deliver the treatments.
A major challenge in Theranostics for the
21st century is to be able to detect
disease biomarkers non-invasively at an
early stage of disease progression and
choose and administer personalized
medical treatment factoring individual
genetic and phenotypic characteristics.
M . A n g e l a k e r i s : N a n o m a g n e t i s m a n d B i o m e d i c a l A p p l i c a b i l i t y 1 3 / 2 3P h y s i c sA U T h
Workshop: Materials at the Nanoscale, 3-4 November, 2018, Thessaloniki-Greece
Hellenic Society for the Science and Technology of Condensed Matter
Issues to considerNanotheranostics
Adjusting the
conditions
From lab to clinical trials
Short & Long term
side effects
Choosing the proper
agent Optimizing the treatment
• biocompatibilty• toxicity• In-vivo
efficiency
the side-effects• Short-term• Long-term• extraction
Optimizing the carrier
• Material Choice• Size• Shape• Magnetic profile• Concentration• Colloidal Stability
the conditions• Frequency• Field intensity
Clinical Application
Colloidal Particles
M . A n g e l a k e r i s : N a n o m a g n e t i s m a n d B i o m e d i c a l A p p l i c a b i l i t y 1 4 / 2 3P h y s i c sA U T h
Workshop: Materials at the Nanoscale, 3-4 November, 2018, Thessaloniki-Greece
Hellenic Society for the Science and Technology of Condensed Matter
NanorobotsNanotheranostics
• Scientists and researchers are discovering new ways that nanotechnology
can be used in the near future. It will be used for drug delivery, treatment
and detection of cancer and other diseases, imaging, and much more.
• One of the more interesting uses of nanotechnology in medicine is the
"nanorobot." The nanorobot is a microscopic robot that can be used
for cancer treatment, drug delivery, or even heart bypass surgery.
• As it enters the bloodstream through a tiny incision and travels through
the many veins and arteries it has the capability of finding specific cancer
cells and treating them.
• This could effectively eliminate the side effects of radiation and
chemotherapy as they would not be needed. Nanorobots could also cut
down on surgery time, recovery time, and the various-side effects related
to procedures such as heart bypass surgery.
M . A n g e l a k e r i s : N a n o m a g n e t i s m a n d B i o m e d i c a l A p p l i c a b i l i t y 1 5 / 2 3P h y s i c sA U T h
Workshop: Materials at the Nanoscale, 3-4 November, 2018, Thessaloniki-Greece
Hellenic Society for the Science and Technology of Condensed Matter
Controlled Drug-releaseNanotheranostics
Cargo can be released in response to
Magnetically triggered drug release system
No cell death is observed prior toapplying a magnetic field.
16% of the cells were killed upon theapplication of an oscillatingmagnetic field without doxorubicinloaded in the pores
When MNPs are loaded with doxo-rubicin and exposed to anoscillating magnetic field, 37% of thecells are killed, with apoptoticbodies indicated by arrows
MDA-MB-231 breast cancer cells
external stimuli:light or a magnetic field
internal stimuli:natural biochemistry
inside cells using redox, enzymes, or a pH change in the cellular
compartments
MNPs which generateheat upon exposure toan oscillatingmagnetic field,causing the CB rings toslip off the stalks, thusreleasing a cargo ofeither rhodamine B ordoxorubicin.
M . A n g e l a k e r i s : N a n o m a g n e t i s m a n d B i o m e d i c a l A p p l i c a b i l i t y 1 6 / 2 3P h y s i c sA U T h
Workshop: Materials at the Nanoscale, 3-4 November, 2018, Thessaloniki-Greece
Hellenic Society for the Science and Technology of Condensed Matter
Nanotheranostics
Controlled Drug-release
M . A n g e l a k e r i s : N a n o m a g n e t i s m a n d B i o m e d i c a l A p p l i c a b i l i t y 1 7 / 2 3P h y s i c sA U T h
Workshop: Materials at the Nanoscale, 3-4 November, 2018, Thessaloniki-Greece
Hellenic Society for the Science and Technology of Condensed Matter
Activation of cell signals
T. R. Pisanic II, Biomaterials 28 2572-2581 (2007)
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.
Under an external magnetic field, magnetic nanoparticles
can move around on cell membrane surfaces and exert
translational forces. Simultaneously, by attaching proper
ligands on MNPs binding of MNPs to special cell-surface
receptors may be achieved and heat-triggered mechanical
stimulations can activate cellular signaling pathways.
a. Clusterisation
b. Translational Force
c. Heat generation
Advantages
a. Spatial
b. Temporal
c. Remote
Control of Cellular ActivitiesMagnetic stimulation in human endothelial cells
Cellular morphology tubular shape = prestage of angiogenesis
Nanotheranostics
M . A n g e l a k e r i s : N a n o m a g n e t i s m a n d B i o m e d i c a l A p p l i c a b i l i t y 1 8 / 2 3P h y s i c sA U T h
Workshop: Materials at the Nanoscale, 3-4 November, 2018, Thessaloniki-Greece
Hellenic Society for the Science and Technology of Condensed Matter
Magnetic HyperthermiaHyperthermia 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.
M . A n g e l a k e r i s : N a n o m a g n e t i s m a n d B i o m e d i c a l A p p l i c a b i l i t y 1 9 / 2 3P h y s i c sA U T h
Workshop: Materials at the Nanoscale, 3-4 November, 2018, Thessaloniki-Greece
Hellenic Society for the Science and Technology of Condensed Matter
Magnetic Hyperthermia
Magnetic implants
+ 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:
Καταπολεμώντας τον καρκίνο με νανοσωματίδιαMagForce: NanoCancer Therapy Fighting Cancer with magnetic
NanoparticlesΗ κεντρική ιδέα της θεραπείας καρκίνου MagForce είναι το
νανοσωματίδιοπου αποτελείται από ένα πυρήνα οξειδίου του σιδήρου και
μια πατενταρισμένη επικάλυψη πουδιασφαλίζει τη χημική σταθερότητα των σωματιδίων και τη
διασποράτους στους προβληματικούς ιστούς (όγκους).Η επικάλυψη αυτή διευκολύνει την προσρόφηση των
νανοσωματιδίων επιλεκτικά από τα καρκινικά κύτταρα,ενώ το μικρό τους μέγεθος είναι καθοριστικής σημασίας για το
θεραπευτικό πρωτόκολλο.Η διάμετρος τους είναι ~ 20 nm και είναι 500 φορές μικρότερη
απόερυθρό αιμοσφαίριο.1 ml από το διάλυμα των σωματιδίων
περιέχειπερίπου 17 τρισεκατομμύρια νανοσωματίδια, καθιστώντας
λειτουργική τη συγκεκριμένη θεραπεία.Στο πρώτο στάδιο της θεραπείας τα νανοσωματίδια εγχέονται
απευθείαςστον όγκο, που στην προκειμένη περίπτωση είναι ένα
γλοιοβλάστωμαένας κακοήθης εγκεφαλικός όγκος, που χαρακτηρίζεται από
επιθετική ανάπτυξη κυττάρων.Σε μικροσκοπικό επίπεδο, διακρίνονται τα υγιή κύτταρα
αριστερά και τα καρκινικά στα δεξιάΜετά την έγχυση τους τα νανοσωματίδια εξαπλώνονται στα
ενδιάμεσα κενά μεταξύ των καρκινικών κυττάρων.Ο ασθενής εισέρχεται σε μια συσκευή παραγωγής μαγνητικών
πεδίων,τα οποία χαρακτηρίζονται εναλλασσόμενα λόγω συχνότητας
(kHz), χωρίς επιπλέον τοξικολογική επιβάρυνση του ασθενούς
Η επίδραση του πεδίου που εναλλάσσει τους πόλους του 100,000 φορές το δευτερόλεπτο πάνω στα μαγνητικά νανοσωματίδιαοδηγεί στην εμφάνισηθερμότητας (μετατροπή μαγνητικής ενέργειας σε θερμική)
δημιουργώντας ένα θερμό περιβάλλονπου καταρχήν ευνοεί την προσρόφηση των νανοσωματιδίων
από τα καρκινικά κύτταρακαι καθώς η θεραπεία επαναλαμβάνεταιτο θερμικό αποτέλεσμα ενισχύεται εμφανώς
ενώ τα νανοσωματίδια αρχίζουν να ταλαντώνονται (ακολουθώντας το εξωτερικό πεδίο οδηγώντας τα καρκινικά κύτταρα σε μηχανισμούς καταστροφήςδιαφορετικής έντασης που τελικά οδηγούν στην πλήρη
αναστολή της ανάπτυξης του όγκου.Η ανάπτυξη του όγκου αναστέλλεται και τα κατεστραμμένα
κύτταρα και τα νανοσωματίδια αποβάλλονταιαπό το σώμα του ασθενούς με φυσικές διαδικασίες. Η μη
επεμβατική αυτή θεραπείαεπαναλαμβάνεται έξι φορές,παρόλο που τα νανοσωματίδια εισέρχονται στον ασθενή μια
φορά στην αρχή της 1ης αγωγής, καθιστώντας τηελάχιστα επιβαρυντική για τον ασθενή.
M . A n g e l a k e r i s : N a n o m a g n e t i s m a n d B i o m e d i c a l A p p l i c a b i l i t y 2 0 / 2 3P h y s i c sA U T h
Workshop: Materials at the Nanoscale, 3-4 November, 2018, Thessaloniki-Greece
Hellenic Society for the Science and Technology of Condensed Matter
To detect small sized pathogenic targets precisely at an early stage, MRI
contrast agents are often used to highlight those specific areas of interest.
One of the most effective ways to increase the MR contrast effects is the
optimization of saturation magnetization (Ms) which is directly related to
the relaxivity coefficient (r2).
Conventional MRI contrast agents are mostly effective only in a single
imaging mode of either T1 or T2 and frequently suffer the ambiguities in
diagnostics especially for small biological targets.
The combination of simultaneously strong T1 and T2 contrast effects in a single contrast
agent can be one of the new breakthroughs, since it can potentially provide more accurate
MR imaging via self confirmation with better differentiation of normal and diseased areas.
D. Yoo et al. Accounts of Chemical Research 44 863 (2011)
Nanotheranostics Contrast Agents in MRI
M . A n g e l a k e r i s : N a n o m a g n e t i s m a n d B i o m e d i c a l A p p l i c a b i l i t y 2 1 / 2 3P h y s i c sA U T h
Workshop: Materials at the Nanoscale, 3-4 November, 2018, Thessaloniki-Greece
Hellenic Society for the Science and Technology of Condensed Matter
Dose-dependent proliferation assay on 3T3 cells bymonitoring the 24-hour cell growth. Normal proliferationrates were obtained at all concentrations tested.
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 magneticsignal from targeted liver at the same time points as imaged by MRI. Maximumconcentrations (~ 90% of the injected dose) were observed 24 hours afterinjection.
Nanomedicine: Nanotechnology, Biology, and Medicine 6 (2010) 362–370
Fe/MgO nanoparticles
Nanotheranostics Contrast Agentsin MRI
M . A n g e l a k e r i s : N a n o m a g n e t i s m a n d B i o m e d i c a l A p p l i c a b i l i t y 2 2 / 2 3P h y s i c sA U T h
Workshop: Materials at the Nanoscale, 3-4 November, 2018, Thessaloniki-Greece
Hellenic Society for the Science and Technology of Condensed Matter
1. Magnetic Nanoparticles directly address the current trends of theranostics since they
combine imaging with therapeutic capabilities and allow a large degree of control
over the treatment efficacy.
2. Magnetism: Effective, Externally stimulated, Specific response to external magnetic field
at cellular level, Easy passage into several tumors .
3. Functionalization: Selective targeting via cancer-binding agents, Multifunctional and
multi-therapeutic approaches.
4. Biocompatibity: Field parameters pass harmlessly through the body, Nanotoxicity
control, efficient and homogeneous treatment with smaller dose.
Biomedical Nanomagnetics: Advances, current trends and challenges
Colleagues
▪ M. Farle, M. Spasova, U. Wiedwald, Germany
▪ Ll. Balcels, C. Boubeta, M. P. Morales, D. Serantes, Spain
▪ K. Chliclia, K. Spriridopoulou, 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
Magnetic Nanostructure Characterization Group:
Technology & Applications
Department of Physics, Aristotle University of Thessaloniki,
54124 Thessaloniki, Greece
http://magnacharta.physics.auth.gr
email: [email protected]