Magnetic Nanoparticles

Question 1

What techniques are used to make NP’s?

Answer 1

Chemical based techniques (synthesis in solutions)
Physical vapour approach (atom by atom)
Electron Beam Lithography (electron carving)
Exploiting nature (bacteria)

Question 2

Outline the life cycle of a magnetic nanoparticle

Answer 2

1. Synthesis of particle and characterisation
2. Surface modification
3. Magnetic guiding to the target
4. Binding at target location
5. Apply alternating magnetic field (therapeutics)
6. Delivery of drug/gene
7. Phagocytosis

Question 3

What is the formulae for magnetic susceptibility?

Answer 3

x= M/H
M= magnetisation
H= an applied magnetic field

Question 4

Explain paramagnetism in terms of spin moments

Answer 4

No magnetic field- spin moments are randomised
Magnetic field- small net magnetism develops through aligning of spin moments resulting in positive magnetic susceptibility

Question 5

Explain ferromagnetism in terms of spin moments

Answer 5

Spin moments coupled together and act over large distance. Retain permanent magnetisation and have large positive magnetic susceptibility.

Question 6

Explain diamagnetisation in terms of spin moments

Answer 6

Magnetic field- small opposing magnetisation in the material (repelled). Small negative magnetic susceptibility

Question 7

Explain magnetic domains

Answer 7

Separated areas of parallel magnetic skin moments.

If particles smaller than a critical diameter, Dc, only a single domain can form. Dc is material dependent.

Question 8

Define remnance

Answer 8

Residual magnetisation

Question 9

What terms is relaxation time given in?

Answer 9

Material constant (the anisotropy constant) K, the particle volume, v, and the temperature, T.

Question 10

Explain the blocked magnetic state

Answer 10

The relaxation time for a given particle is much longer than our measurement time

Question 11

Explain the superparamagnetic state

Answer 11

The relaxation time for a given particle is much shorter than our measurement time

Question 12

Why do superparamagnets have a higher magnetic susceptibility than paramagnets?

Answer 12

The magnetic field aligns whole particle moments

Question 13

What are the properties of a useful magnet?

Answer 13

Strong magnetic susceptibility
Zero remanence
Well matched relaxation times

Question 14

What are the functions of thermotherapy?

Answer 14

Raise local temperature in tumours
Deactivation of normal cellular processes
Increase therapeutic effect of other treatment
Can be modified to target a specific tissue

Question 15

Properties of nanoscale superpara particles

Answer 15

Small enough for admin
Must reside in vivo long enough to reach target
Avoid immunological reactions
Longer plasma half life
No residual magnetism when magnet removed
Do not agglomerate

Question 16

Name some polymers that modify the surface of nanoparticles

Answer 16

Polyethyleneglycol
Dextran, PVP
Polypeptides
Chitosan
Gelatin

Question 17

Name some targeting ligands used for functionalising nanoparticles

Answer 17

Transferrin
Insulin
Elastin
Tat-peptide

Question 18

How does MRI enable measurements of signal variation?

Answer 18

The receiver coil measures transverse magnetisation but is not stable
Longitudinal relaxation and transverse relaxation
Altering time at which signal is measured by utilizing variations in relaxation processes

Question 19

How do ferromagnet contrast agents work?

Answer 19

They change the contrast by distorting the magnetic field around ferromagnetic material in the contrast agent. Typically FeO NP’s attached to organic substrate

Question 20

How do paramagnetic contrast agents work?

Answer 20

Create time varying magnetic fields which promote spin-lattice and spin-spin relaxation of water molecules

Question 21

What are the difficulties with mechanical conditioning in bioreactors?

Answer 21

Interruption of nutrient flow to apply force
Invasive processes can comprise sterility
Scaffolds must be strong
Forces must be transmitted to cells rather than applied directly
Limitations on size of constructs

Question 22

What are the advantages of the MICA system?

Answer 22

Application of mechanical stress
Removes requirement for fixed dimension
Allows the use of mechanically weak scaffold materials
Reduced infection potential
Control of physical stress parameters
Allows for multiple load profile to be assigned across complex tissue

Question 23

What are the stages if ex vivo transgene delivery?

Answer 23

1. target cells removed form patient
2. cells grown in culture
3. cultured cells are transfected
4. cells reintroduced into the body
5. Inside the body, the cells produce the desired proteins

Question 24

What are the stages if in vivo transgene delivery?

Answer 24

1. copies of therapeutic gene are insrted into viral DNA, liopsome or in form of plasmid DNA
2. genetically-altered DNA is inserted into patient body by cell-specific direct tissue injection
3. DNA incorporated into cells of specific tissue it was injected into.

Question 25

What are the goals for delivering material into cells?

Answer 25

Don't kill the cell outright Don't damage the cell so that it can't recover Don't adversely change the cell Controllably deliver the material to the cell Delivery vector can't be toxic Safe and efficient

Question 26

What are the advantages and disadvantages of non-viral transfection?

Answer 26

Advantages: Eliminates safety concerns Variety of techniques to choose from Can be used for large groups of cells or individual cells Disadvantages: Less efficient than viral transfection Technically demanding No best method for all applications

Question 27

Explain the Luciferase assay

Answer 27

1. Luciferase first extracted from transfected cells via cell lysis 2. Buffer and additional components added to lysate to increase sensitivity and maintain pH 3. The luminescent reaction is then triggered by an injection of luciferin 4. Emitted light is recorded

Question 28

What does magnetofection rely on?

Answer 28

Selection of appropriate type, size and surface coating of the magnetic nanoparticles for binding with genetic materials. Attach to surface by cleavable linkers and utilising electrostatic interactions.

Question 29

How do magnetic materials generate heat inside the body?

Answer 29

Alternating magnetic field Movement of magnetic domain walls Phase lag between the magnetisation vector and field Eddy currents: negligible effect at frequencies of interest

Question 30

How is heat generated in larger particles?

Answer 30

Due to losses in magnetic energy during hysteresis cycling

Question 31

How is heat generated in smaller particles?

Answer 31

Due to a phase lag between the applied frequency and the particle magnetization vector

Question 32

What are the two types of relaxation that produce heat?

Answer 32

``` Brownian relaxation (rotation of particles) which is dependent on particle size Neel relaxation (internal fluctuations) which is dependent on particle size and magnetic material properties ```

Question 33

What is dynamic light scattering (DLS) used for?

Answer 33

Measuring particle sizes and their distributions in solution based on the fact that smaller particles will diffuse faster than larger particles

Question 34

Why is hyperthermia effective?

Answer 34

It is possible to kills cells at temps between 39-42 Tumour tissue more thermally sensitive than normal tissue due to its vasculature Can reverse chemosresistance increases tumour oxygenation

Question 35

What are the basic principles of MRI?

Answer 35

1. A strong magnetic field is used to align proton spins 2. A radio frequency pulse briefly rotates the alignment by 90 degrees into the xy plane 3. The magnetisation in this plane is detected as a signal in receiving coils

Question 36

What is T1 and T2?

Answer 36

``` T1= Longitudinal Relaxation T2= Transverse relaxation ```