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Lab 3 > Nanoparticles in Diagnostics & Imaging + Tissue Engineering > Flashcards

Nanoparticles in Diagnostics & Imaging + Tissue Engineering Flashcards

1
Q

medical diagnosis = process of determining what?

A

which disease/ condition explains a persons symptoms and signs

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2
Q

Why are nanoparticles used in imaging?

A

Overcome limitations of small molecules

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3
Q

What are some examples of small molecules used in clinical practice?

A

FDG, iodinated molecules, chelated gadolinium

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4
Q

whats FDG used for?

A

PET scan

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5
Q

what are iodinated small mols used for?

A

CT scan

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6
Q

whats chelated gadolinium used for?

A

MRI

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7
Q

What are some limitations of small molecules as imaging agents?

A

Low signal intensity, poor stability, nonspecific interactions, rapid clearance

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8
Q

What advantages do nanoparticles have as imaging agents?

A

Increased signal intensity, stable imaging signals, can coat with multiple ligands

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9
Q

What is PET imaging used for?

A

Detecting cancer metastasis

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10
Q

How do PET scans work?

A

Detects pairs of gamma rays emitted indirectly by
a positron- emitting radionuclide

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11
Q

What is CT imaging used for?

A

Preventive medicine, screening for disease, colonography, heart scans

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12
Q

How do CT scans work?

A

computer generation of X-RAY measurements to produce a cross-sectional (tomographic) images

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13
Q

What is MRI imaging used for?

A

Preoperative staging of rectal and prostate cancer

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14
Q

How do MRI scans work?

A

strong magnetic fields, magnetic field gradients, and radio waves to generate images of the organs in the body

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15
Q

why do we use nanoparticles in IMAGING?

A

high avidity as they can be coated with multiple ligands
allow multiple bond interactions
= nanoparticle accumulation at tumour site
= increase signal-to-noise ratio
longer circluation
= allows repeated imaging

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16
Q

why is NP use in imaging -> increased signal-to-noise ratio useful?

A

allows cancerous tissue to be better highlighted relative to adjacent normal tissue

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17
Q

What is the meaning of high avidity in nanoparticles?

A

They can be coated with multiple copies of ligands

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18
Q

what is the photoacaoutic/ optoacoustic effect?

A

formation of sound waves following light absorption in material sample

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19
Q

What is the rationale for using nanoparticles in DIAGNOSTICS?

A

Can be taken up by cells
Can be targeted to different diseases sites - EPR/active

DDS can be used for theranostic applications

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20
Q

what can you do to NPs for active targeting?

A

attach moieties to surface - antibodies/ fragments

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21
Q

What is the active ingredient in a pregnancy test that gives the indicator strip its colour?

A

Gold nanoparticles

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22
Q

What is the hormone detected in a pregnancy test?

A

Human chorionic gonadotropin (hCG)

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23
Q

What is hCG?

A

Peptide polymer of 244 amino acids, excreted in urine after fertilized egg implants in uterus, detected with 99% accuracy

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24
Q

What are the components of a pregnancy test?

A

Plastic housing, absorbent tip, immunoassay strip, gold nanoparticles, monoclonal antibodies

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25
Q

when are gold NP’s used?

A

diagnostic
testing for pregnancy
attached with monoclonal antibody for hCG
once attach n travelled = strip activated

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26
Q

What are gold nanoparticles?

A

Active ingredient in pregnancy test, appear red due to interaction with light, give indicator strip its color, monoclonal antibodies: designed to identify hCG, attach themselves to gold is hCG present, move up strip until reach indicator

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27
Q

What is the clinical use of iron oxide nanoparticles (SPIONS)?

A

MRI contrast agents used in clinic

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28
Q

what are SPIONS

A

Small nanomaterials consisting of iron oxide core crystals surrounded by a stabilising polymer or polysaccharide shell

2 most commonly studied iron oxides have been
magnetite (Fe2O4) and maghemite (g-Fe2O3)

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29
Q

T/F no need to use ionising radiation w MRI?

A

true

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30
Q

what are MRI contrast agents?

A

group of contrast media used to improve visibility of internal body structure in MRI

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31
Q

what is the most common MRI contrast agents?

A

gadolinium-based OMNISCAN

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32
Q

what drug classification are MRI contrast agents known as?

A

T1 or T2 agents

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33
Q

How are SPIONs used as contrast agents for MRI of infection and inflammation?

A

Phagocytosis by macrophages of injected SPIONs -> hypo-intensity of macrophage-infiltrated tissues in contrast-enhanced MR images.

SPIONs as contrast agents are useful for the in vivo MRI detection of macrophage infiltration.

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34
Q

Why are most nanoparticle imaging agents not cleared renally?

A

They are larger than 10 nm

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35
Q

how can spion use/ detection of macrophage infiltration be useful?

A

SPIONs used as MRI contrast agents can be used to detect inflammation and infection therefore help used to detect severe arthritis and osteomyelitis
- inflammation of bone/bone marrow

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36
Q

What is osteomyelitis?

A

Inflammation of bone or bone marrow, usually due to infection.

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37
Q

What can SPIONs be used to detect?

Why is it particularly a good marker?

A

Active infection in patients with septic arthritis and osteomyelitis.

MRI signal intensity of tissue
Returns to normal value after successful treatment.

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38
Q

What is the importance of the MRI signal intensity of the tissue returning to its un-enhanced value?

A

It indicates successful treatment of the infection.

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39
Q

What is the ability of SPION-enhanced MRI?

A

provides the ability to distinguish the inflamed pancreas of type 1 diabetes mellitus patients from that of normal control subjects, a finding that was based on the infiltration of the pancreatic islets by macrophages.

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40
Q

What is SPECT/CT?

A

Single photon emission computed topography where two different types of scans are taken and the images or pictures from each are fused or merged together.

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41
Q

what can SPECT/CT be used for?

A

identifying tumours (lumps) and alzheimer’s disease

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42
Q

Why is a SPECT/CT scan better than trasiitonal imaging methds?

A

Provides more precise information on body function and can identify tumours and Alzheimers disease.

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43
Q

T/F
spect is a non-invasive nuclear imaging test

A

true
it uses radioactive tracers that are injected into blood

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44
Q

what is administered in SPECT/CT?

A

MWNT-DPTA[111In]
IV

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45
Q

What 2 radio-filled carbon nanotubes are used in lung imaging?

A

SWNT filled with Iodine 125.
Glycosylated SWNT

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46
Q

What are quantum dots?

A

Tiny semiconducting particles with diameters of 2-10 nm.
can be excited to fluoresce.

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47
Q

name examples of quantum dots?

A

cadmium selenide (high tox!)
fluorescent NPs

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48
Q

What determines the color of light emitted from quantum dots?

A

The size of the particle

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49
Q

What colour do smaller quantum dots appear?

A

blue

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50
Q

What colour do larger quantum dots appear?

A

red

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51
Q

cadmium selenide PK effects

A

A semiconducting material used to make quantum dots.
=toxic

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52
Q

what are quantum dots used for?

A

cancer diagnosis
sentinel lymph nodes (SLN) mapping

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53
Q

What is a sentinel lymph node?

A

first lymph node/s to which cancer cells are most likely to spread from a primary tumour

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54
Q

how are sentinel lymph nodes (SLN) detected?

A

using near-infrared (NIR) fluorescent quantum dots

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55
Q

What is the purpose of analyzing a sentinel lymph node?

A

To determine if cancer cells have spread from a primary tumor.

56
Q

What is near-infrared (NIR) fluorescence imaging?

A

A technique that uses quantum dots to visualize lymphatic flow.

57
Q

What is the signal-to-background ratio?

A

The ratio of the signal from the quantum dots to the background autofluorescence.

if background autoflourescene is low, = high s-t-b-ratio

58
Q

What is the size and sex of the rats used in SLN mapping?

A

300-350 g, either sex.

59
Q

What is the injection site in SLN mapping?

A

The site of the primary tumor.

60
Q

What is MSOT?

A

Multispectral optoacoustic tomography for whole-body imaging of biochemical markers in small animals.

61
Q

How does MSOT work?

A

illuminates tissue with light pulses at multiple wavelengths and detects the acoustic waves generated by the thermoelastic expansion of the environment surrounding absorbing molecules.

62
Q

What are acoustic waves?

A

Type of longitudinal waves that propagate by means of adiabatic compression and decompression.

63
Q

What does adiabatic mean?

A

without transfer of heat or matter

64
Q

what are acoustic waves ? and when are they used?

A

sound
longitudinal waves

for MSOT

65
Q

What is the advantage of MSOT?

A

allows high-resolution imaging of photo-absorbers deep within tissue, beyond the classical depth and resolution limitations of conventional optical imaging.

66
Q

What are gold nanoparticles?

A

Nanoparticles that exhibit strong optoacoustic responses due to plasmon resonance.

67
Q

Why are gold nanoparticles not really clinically accepted in MSOT?

A

Long retention times in tissues.

but still provide good signal strength and photo-stability.

68
Q

Why are gold nanoparticles still used?

A

They remain the current standard for signal generation in optoacoustic imaging due to their excellent signal strength and photo-stability.

69
Q

what is indocyanine green (ICG)?

A

cyanide dye used in medical diagnostics

70
Q

What does indocyanine green determine? uses

A

cardiac output
hepatic function
liver blood flow
ophthalmic angiography

71
Q

What is the peak spectral absorption of ICG?

A

About 800 nm.

72
Q

how does indocyanine green (ICG) work?

A

infrared frequencies penetrate retinal layers, allowing ICG angiography to image deeper patterns of circulation

ICG binds tightly to plasma proteins and becomes confined to the vascular system

73
Q

What happens to ICG once it binds to plasma proteins?

A

It becomes confined to the vascular system. :(

74
Q

What is the half-life of ICG?

A

short
150 to 180 seconds.

75
Q

How is ICG removed from circulation?

A

Exclusively by the liver to bile juice.

76
Q

how are ICG administered?

A

encapsulated in a liposome

77
Q

Solubility Of 5% Dextrose Solution Containing ICG In Water?

A

will be soluble in water bc both dextrose and ICG are water-soluble compounds. Dextrose, also known as glucose, is a simple sugar that is highly soluble in water, while ICG is a water-soluble dye that dissolves readily in aqueous solutions.

Therefore, when a 5% dextrose solution containing ICG is mixed with water, the ICG will dissolve in the water along with the dextrose

78
Q

what is the advantage of encapsulating ICG? and what in?

A

LipoICG - in a liposome

acts as:
highly potent optoacoustic agent
high sensitivity and resolution to show vascularisation

79
Q

What is ICG?

A

A fluorescent dye
used in imaging

80
Q

What tumor model was used?

A

4T1 murine tumor model known for its fast growth

81
Q

name a theranostic agent

A

Arginylglycylaspartic acid (RGD)

82
Q

what is Arginylglycylaspartic acid (RGD)?

A

a theranostic agent
tripeptide composed of L- arginine, glycine and L-aspartic acid

83
Q

What is the role of RGD-peptides?

A

Implicated in cellular attachment via integrins.

84
Q

What is the MTT assay?

A

Assay to determine cytotoxicity.

85
Q

Where do the SPIO nanocarriers accumulate primarily?

A

In the tumor and liver but not in most normal tissues.

85
Q

Where do the SPIO nanocarriers accumulate primarily?

A

In the tumor and liver but not in most normal tissues.

86
Q

Why are nanoparticles used in imaging and diagnostics?

A

Due to their intrinsic properties.

87
Q

Encapsulation of existing fluorophores within soft or hard drug delivery systems can provide additional benefits, such as:

A

Protection of the fluorophore from degradation or quenching

Controlled release of the fluorophore for sustained imaging over time

Simultaneous imaging and drug delivery for theranostic applications

88
Q

What are CLSM images?

A

Confocal laser scanning microscopy images.

To show U87MG cells treated with different nanocarriers and free DOX.

89
Q

Tissue engineering…

what is the goal of tissue engineering?

A

replace/improve biological tissue and their functions

different tissue artificially made/formed into bone/vessels/bladder/muscle

90
Q

What are the four factors of tissue engineering?

A

Scaffold.
Living cells/tissue.
Control over growth factors.
Culturing.

91
Q

what is scaffolding in tissue engineering?

A

supporting tissue formation in 3D space

92
Q

what does culturing include in tissue engineering?

A

maintain oxygen/pH/humidity/temp/nutrients/osmotic pressure

93
Q

What are the basic principles of tissue engineering?
5 steps

A

Remove cells from the body.
Cell expansion in culture.
Seed the cultured cells on scaffolds in culture media.
Leave to form functional tissue.
Re-implant.

94
Q

Seed the cultured cells on scaffolds in culture media supplemented with what?

A

growth factors

95
Q

what kind of scaffolds will you need in the culture media?

A

those that recapture the extracellular matrix (ECM) and microenvironment to match where the injury site is

96
Q

why do biomed nanomaterials play central role in tissue engineering?

A

as they may better support tissue regeneration

97
Q

What are the 3 criteria for nanomaterials used as scaffold in tissue engineering?

A

Biocompatibility
Biodegradability
Low immunogenicity

98
Q

What happens if incompatible biomaterials are used as scaffolds in tissue engineering?

A

Leads to an inflammatory response or foreign-body-reaction that eventually leads to rejection and/or necrosis.

99
Q

smart biomaterial scaffold can maintain adequate mechanical integrity and simultaneously do what?

A

accelerate tissue formation during early stages of development

100
Q

What does a scaffold made from nanoscaled fibres provide?

A

Good cellular interactions and tissue compatibility

101
Q

What feature allows these nano materials to have good cellular interactions?

A

increased ratio of surface area to volume

improve mimicking of EC environment

102
Q

What architectural properties contribute to tissue repair in terms of cell-material interactions?

A

porosity and surface features

103
Q

biodegradability + biocompatibility are desirable to increase what?

A

success rate of implantation of a connstruct

104
Q

biodegradability + biocompatibility are desirable to avoid what?

A

additional surgocal procedures and A SEs

105
Q

biodegradability + biocompatibility are desirable but alos consider degradation of these materials why?

A

employed as additional infiltration path for cells/ as release mechanism for bioactive mols stored in scaffold

106
Q

T/F
proper cell infiltration is vital

A

true
for cell migration, prolif, diff in scaffold

107
Q

What should a good scaffold also do in tissue engineering?

A

Support cells.

Regulate the extracellular environment to enhance tissue alignment an cell-cell interactions.

108
Q

what does a good scaffold lead to for the cell?

A

sufficient neovascularisation, adequate oxygen supply, and mechanism for waste disposal

without these, regenrated tissue will not function properly

109
Q

selection of appropriate nanomaterial has significant impact on what?

A

functional tissue regeneration

110
Q

advantages of metallic nanostrutures

A

optical adjustability
electrical conductivity
surface chemistry
ease of fabrication

111
Q

Give an example of how metallic nanostructures are used clinically

A

engineered cardiac patches for treating damaged heart tissue after a heart attack.

112
Q

what are engineered cardiac patches used for?

A

treating damaged heart tissues after a heart attack

113
Q

how are engineered cardiac patches made? of

A

biological polymers - alginate /synthetic polymers
such as poly(lactic) acid (PLA)

114
Q

what are engineered cardiac patches made of ?

A

metallic nanostructure

115
Q

What limits cardiac patches made from metallic nanostructures from contracting strongly as a unit?

A

poor conductivity of the biological polymers used as scaffolds

116
Q

Why might gold nanowires be used with alginate scaffolds?

A

enhances electrical communication and tissue thickness.

117
Q

what does gold nanowires incorporated into alginate scaffolds show?

A

the cells in this tissue have shown the ability to contract synchronously corresponding to electrical stimuli

increased chance of contraction

118
Q

name 3 materials used in metallic nano materials in tissue engineering?

A

gold, silver and titanium/Ti6Al4V

119
Q

How are carbon nanotubes CNTs used in tissue engineering?

A

Cardiopulmonary applications as catheters.
neuronal tissue regeneration

120
Q

Benefits of using carbon nanotubes in tissue engineering?

A

highly compatible with blood.
chemically inert.
neuronal tissue regeneration due to superior electrical conductivity = promote neurone attachment/growth /differentiation and long-term survival

121
Q

what CNTs combines with to enhance its strength and elongation capacity?

A

polyurethane

122
Q

what happens when CNTs are integrated into polyurethane?

A

enhance its strength and elongation capacity
anticoagulant properties

123
Q

Why are cells encapsulated in tissue engineering?

A

prevent immune cells/antibodies from destroying

overcome existing problems of graft rejection

reduce need for immunosuppressive drugs after an organ transplant to control side effects = reduce polypharmacy

124
Q

Why are cells encapsulated in tissue engineering? 2

A

To overcome graft rejection.
Reduce need for long term immunosuppressants.

125
Q

cell encapsulation: cells immobilised in polymeric semi-permeable membrane which permits what type of diffusion of mols such as influx of O2, nutrients, GF?

A

bidirectional

but semi perm membrane prevents immune cells and abtibodies destroying encapsulated cells

126
Q

what are engineered cells encapsulated in?

A

polymeric semi-permeable membrane

127
Q

when is collagen used in tissue engineering?

A

in the ECM
abundant mammal protein
to provide support to tissues - skin/cartilage/bones/blood vessels/ ligaments

128
Q

Why is collagen a good model scaffold for tissue engineering?

A

Biocompatibility
Biodegradability
Ability to promote cell binding.

129
Q

What properties facilitate printability for 3D bioprinting?

A

viscosity
gelation methods
rheological properties

130
Q

what is biomimicry?

A

involves manufacture of identical reproductions of cellular and EC components of tissue/ organ

131
Q

whats autonomous self assembly?

A

relies on cell as prim driver of histogenesis, directing composition, localisation, functionalisation, sstructural properties of tissue

132
Q

example of a mini tissue?

A

kidney nephron

133
Q

What must be considered in terms of biocompatibility in bioprinting?

A

materials should not induce local or systemic responses from host

134
Q

What must be considered in terms of degradation in bioprinting?

A

degradation rates should match the cell’s ability to produce their own extracellular matrix

non-toxic

suitable swelling or contraction

135
Q

Give examples of how bioprinting has been used on a human scale

A

skin
cartilage
aortic valves

136
Q

how are cells regrown?

A

3D bioprinting has been used

Lab 3 (21 decks)

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