2. Magnetic nanoparticles
• Nanoparticles are defined as ‘solid colloidal particles ranging in size from 10
to 1000 nm (1 μm). Nanoparticles are used in biomedical applications as they
offer many advantages to larger particles such as increased surface to volume
ratio and increased magnetic properties
• The first time, the magnetic fluids were prepared with magnetite nanoparticles
at 1960 by NASA
• On the other hand, by developing the nanotechnology (particle size < 100 nm)
in the last decades, the magnetic nanoparticles have found the special
importance in the modern purposes like biomedical sciences caused by their
unique characteristics.
2
3. Figure 1: The increasing number of articles related to biomedical
applications of magnetic nanoparticles based on Elsevier database.
3
5. Properties of Magnetic nanoparticles (MNPs) that should be used in
bio medical applications
1. Large surface area to volume ratio.
2. The possibility to access in all kind of biological tissues.
3. Biocompatibility and relatively low toxicity in human body.
4. Less sensitivity to oxidation.
5. More stability in magnetic response.
6. Ease of synthesis process and surface treatment ( low coast).
7. The dispersed ultra-fine magnetite particles should be stabilized in
aqueous or other organic fluids.
5
6. 8. Possibility of transfer to superparamagnetic Form by particle size
decreasing (ferri/ferromagnetic nanoparticles have single-domain
structure and superparamagnetic behavior).
9. Have a long blood circulation time, thus provider greater time for
specific localization.
10.Collide stability in biological environments especially vivo media.
11.Low agglomeration probability after applying magnetic field so their
movement in blood and extraction easier.
6
7. • Most of researches in magnetic bio medical application
based on using super para magnetic particles SPMPs and
especially magnetite particles, so
• What is the magnetite ?
• What is the super para magnetic phenomena in
nonmagnetic particles ?
Super para magnetic particles (SPMPs)
7
8. magnetite (Fe3O4)
is the most commonly used form for biomedical applications.
However, this form of iron oxide has a tendency to oxidize so
coating with a biocompatible shell is required. Some examples of
coatings include polymers, ceramics and metals. Coating with a
shell offers many advantages such as it prevents agglomeration
and helps with further functionalization and conjugation to
proteins, enzymes, antibodies and anticancer drugs. Iron oxide
nanoparticles have been investigated for use in magnetic.
8
9. Super para magnetism phenomena
• Superparamagnetism is a form of magnetism which appears in small
ferromagnetic or ferrimagnetic nanoparticles. In sufficiently small nanoparticles,
magnetization can randomly flip direction under the influence of temperature. The
typical time between two flips is called the Néel relaxation time. In the absence of
an external magnetic field, when the time used to measure the magnetization of
the nanoparticles is much longer than the Néel relaxation time, their magnetization
appears to be in average zero; they are said to be in the superparamagnetic state. In
this state, an external magnetic field is able to magnetize the nanoparticles,
similarly to a paramagnet. However, their magnetic susceptibility is much larger
than that of paramagnets.9
10. • In the absence of magnetic field the particle behave like a para
magnetic material but with the Presence of the magnetic field the
particle behave like a ferromagnetic material.
• SPMPs do not depend on curie temperature but depends on blocking
temperature Tb
In SP materials, particles become a single domain and have higher
magnetic susceptibility than paramagnetic materials.
10
12. The deference between ferromagnetic and super para magnetic materials in
behavior with/without applying an external magnetic field12
13. The details of superparamagnetic behavior as a function of blocking temperature
and relaxation time. In state (i), temperature is below the blocking temperature
and the anisotropy energy is dominated to the thermal energy; so, the moments
are apparently fixed. In state (ii), temperature is higher than blocking point and
the thermal energy is larger than anisotropy one; thereby, the superparamagnetic
structure is formed.13
14. The schematic of magnetic relaxation mechanisms such as Neel and Brownian relaxation
mechanisms
14
16. The variation of thermal and anisotropy energies by particles resizing from large
scale (ferri/ferromagnetic structure) to fine nanoscale (superparamagnetic structure).
16
19. Properties of Superparamagnetic particles (SPMPs)
1. Particle size less than 30 nm
2. Single domain structure.
3. Should have a high value of saturation magnetization (𝑀s) and
minimum value of coercive field (𝐻c)
4. High magnetic susceptibility.
5. High magneto – crystalline an isotropy.
6. The M – H curve in these material has sigmoidal shape (S shape)
without any hysteresis loop (leave behind zero residual magnetization
after an external magnetic field is removed).
19
22. magnetic hyperthermia treatment
• Magnetic hyperthermia treatment treats tumors by heating them to
above 42 °C to destroy the cancerous cells
• The benefit of this technique over chemotherapy is that it specifically
targets the tumor and does not damage the surrounding healthy tissue.
• The temperature of the infected or diseased area is raised to 41–46 °C
to kill the cancerous cells without damaging the healthy cells.
• Cancerous cells have a higher sensitivity to temperature than healthy
cells referred to as thermos ablation.
22
23. • In hyperthermia application, the nanoparticles form a Ferro fluid in the
blood, move and rotate randomly in the fluid, exhibiting Brownian
motion. When a magnetic field is applied to them.
• Magnetic nanoparticles rotate and align with the magnetic field.
• The magnetization of nanoparticles can spontaneously change their
orientation under the influence of thermal energy by phenomenon
called superparamagnetism.
• The magnetization of the nanoparticle is also reversed when an applied
magnetic field is large enough to suppress the energy barrier between
the two equilibrium positions, a phenomenon which is known as the
Stoner–Wohlfarth model of magnetization reversal.
23
25. Magnetic Resonance Imaging (MRI)
The aim of the use of magnetic nanoparticles for MRI and compute
tomography is as contrast agents for bio imaging techniques.
Magnetic Resonance Imaging (MRI) is one of the most powerful and a
noninvasive technique that uses magnetic fields to produce high resolution
and high-contrast images of tissue structure and function.
The major advantage of MRI is the detectability of soft tissues like muscles,
blood flow in vessels, and the density of each tissue in body.
In general, foundation of MRI mechanism based on the alignment of
unpaired magnetic spins of tissues to the applied magnetic field direction.
25
38. In fact, many tissues of body contain more than 70% water (with
different densities in various tissues); thus, according to the electron
configuration of hydrogen atoms in the water molecules that is /1S1 /,
a large number of unpaired spins are variously reacted to the applied
field in each tissue.
In MRI device, the aligned spins are diverted from field direction by
applying radio frequency (RF) signals and then they will returned to
initial alignment by removing RF pulses
The MR images formed based on the returning time contrast of
different tissues.
38
39. These returns that are called relaxation and divided into Two
independent relaxation processes, longitudinal relaxation (T1-
recovery) and transverse relaxation (T2-decay), can be occur to
generate an MR image.
Conventional Gd3+ or Mn2+ complexes, belonging to the T1 contrast
agents, may display toxicity.
39
40. But MNPs with improved efficiency and biocompatibility, belonging to the
T2 contrast agents is the revolution of the century as a contrast agent
because
a. MNPs have a long circulation time up to 24 h
b. non-toxic
c. low magnetic field requirement
d. decrease T2 relaxation time so it will increase relaxation rate hence we can
get a high resolution image
40
41. Figure : The schematic of 𝑇1 and 𝑇2 relaxations mechanisms. (a) The schematic of 𝑇1
recovery mechanism and (b) the schematic of 𝑇2decay mechanism.
41
46. Targeted drug delivery
• Targeted drug delivery is an important biomedical application that aims to
deliver anticancer drugs to the specific site of the tumor and avoid damage to
surrounding healthy cells. Currently, iron oxide nanoparticles are the main
source of magnetic materials being used to deliver anticancer drugs to target
specific areas.
• Generally, the magnetic nanoparticles are coated with a biocompatible layer,
such as gold or polymers, this is done to functionalize the nanoparticles so
that the anticancer drug can either be conjugated to the surface or
encapsulated in the nanoparticle as shown in Figure below.
• Once the drug/nanoparticle complex is administered, an external magnetic
field is used to guide the complex to the specific tumor site. The drug is
released by enzyme activity or by changes in pH, temperature or osmolality.
46
47. Fig: Diagram of targeted drug delivery using magnetic nanoparticles.
47
49. Figure: The schematic of some possible structures of inorganic coatings such as
core-shell, matrix (mosaic), shell-core, and shell-core-shell structures
49
50. cell separation and DNA detection
Schematic representation of magnetic separation of DNA or proteins in solution. The grey rods
on the surface of the spherical MNP represent the immobilized tag, which will tightly bind the
DNA strand or protein of interest. The separation process follows the steps: (A) MNPs and the
solution with different components are mixed, (B) particular proteins or DNA (green rings) bind
to the MNPs and (C) magnetic field is applied to trigger magnetic decantation, followed by
further washing steps and collecting the molecule of interest.50