Nanoparticles in Diagnostics & Imaging + Tissue Engineering Flashcards
medical diagnosis = process of determining what?
which disease/ condition explains a persons symptoms and signs
Why are nanoparticles used in imaging?
Overcome limitations of small molecules
What are some examples of small molecules used in clinical practice?
FDG, iodinated molecules, chelated gadolinium
whats FDG used for?
PET scan
what are iodinated small mols used for?
CT scan
whats chelated gadolinium used for?
MRI
What are some limitations of small molecules as imaging agents?
Low signal intensity, poor stability, nonspecific interactions, rapid clearance
What advantages do nanoparticles have as imaging agents?
Increased signal intensity, stable imaging signals, can coat with multiple ligands
What is PET imaging used for?
Detecting cancer metastasis
How do PET scans work?
Detects pairs of gamma rays emitted indirectly by
a positron- emitting radionuclide
What is CT imaging used for?
Preventive medicine, screening for disease, colonography, heart scans
How do CT scans work?
computer generation of X-RAY measurements to produce a cross-sectional (tomographic) images
What is MRI imaging used for?
Preoperative staging of rectal and prostate cancer
How do MRI scans work?
strong magnetic fields, magnetic field gradients, and radio waves to generate images of the organs in the body
why do we use nanoparticles in IMAGING?
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
why is NP use in imaging -> increased signal-to-noise ratio useful?
allows cancerous tissue to be better highlighted relative to adjacent normal tissue
What is the meaning of high avidity in nanoparticles?
They can be coated with multiple copies of ligands
what is the photoacaoutic/ optoacoustic effect?
formation of sound waves following light absorption in material sample
What is the rationale for using nanoparticles in DIAGNOSTICS?
Can be taken up by cells
Can be targeted to different diseases sites - EPR/active
DDS can be used for theranostic applications
what can you do to NPs for active targeting?
attach moieties to surface - antibodies/ fragments
What is the active ingredient in a pregnancy test that gives the indicator strip its colour?
Gold nanoparticles
What is the hormone detected in a pregnancy test?
Human chorionic gonadotropin (hCG)
What is hCG?
Peptide polymer of 244 amino acids, excreted in urine after fertilized egg implants in uterus, detected with 99% accuracy
What are the components of a pregnancy test?
Plastic housing, absorbent tip, immunoassay strip, gold nanoparticles, monoclonal antibodies
when are gold NP’s used?
diagnostic
testing for pregnancy
attached with monoclonal antibody for hCG
once attach n travelled = strip activated
What are gold nanoparticles?
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
What is the clinical use of iron oxide nanoparticles (SPIONS)?
MRI contrast agents used in clinic
what are SPIONS
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)
T/F no need to use ionising radiation w MRI?
true
what are MRI contrast agents?
group of contrast media used to improve visibility of internal body structure in MRI
what is the most common MRI contrast agents?
gadolinium-based OMNISCAN
what drug classification are MRI contrast agents known as?
T1 or T2 agents
How are SPIONs used as contrast agents for MRI of infection and inflammation?
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.
Why are most nanoparticle imaging agents not cleared renally?
They are larger than 10 nm
how can spion use/ detection of macrophage infiltration be useful?
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
What is osteomyelitis?
Inflammation of bone or bone marrow, usually due to infection.
What can SPIONs be used to detect?
Why is it particularly a good marker?
Active infection in patients with septic arthritis and osteomyelitis.
MRI signal intensity of tissue
Returns to normal value after successful treatment.
What is the importance of the MRI signal intensity of the tissue returning to its un-enhanced value?
It indicates successful treatment of the infection.
What is the ability of SPION-enhanced MRI?
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.
What is SPECT/CT?
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.
what can SPECT/CT be used for?
identifying tumours (lumps) and alzheimer’s disease
Why is a SPECT/CT scan better than trasiitonal imaging methds?
Provides more precise information on body function and can identify tumours and Alzheimers disease.
T/F
spect is a non-invasive nuclear imaging test
true
it uses radioactive tracers that are injected into blood
what is administered in SPECT/CT?
MWNT-DPTA[111In]
IV
What 2 radio-filled carbon nanotubes are used in lung imaging?
SWNT filled with Iodine 125.
Glycosylated SWNT
What are quantum dots?
Tiny semiconducting particles with diameters of 2-10 nm.
can be excited to fluoresce.
name examples of quantum dots?
cadmium selenide (high tox!)
fluorescent NPs
What determines the color of light emitted from quantum dots?
The size of the particle
What colour do smaller quantum dots appear?
blue
What colour do larger quantum dots appear?
red
cadmium selenide PK effects
A semiconducting material used to make quantum dots.
=toxic
what are quantum dots used for?
cancer diagnosis
sentinel lymph nodes (SLN) mapping
What is a sentinel lymph node?
first lymph node/s to which cancer cells are most likely to spread from a primary tumour
how are sentinel lymph nodes (SLN) detected?
using near-infrared (NIR) fluorescent quantum dots
What is the purpose of analyzing a sentinel lymph node?
To determine if cancer cells have spread from a primary tumor.
What is near-infrared (NIR) fluorescence imaging?
A technique that uses quantum dots to visualize lymphatic flow.
What is the signal-to-background ratio?
The ratio of the signal from the quantum dots to the background autofluorescence.
if background autoflourescene is low, = high s-t-b-ratio
What is the size and sex of the rats used in SLN mapping?
300-350 g, either sex.
What is the injection site in SLN mapping?
The site of the primary tumor.
What is MSOT?
Multispectral optoacoustic tomography for whole-body imaging of biochemical markers in small animals.
How does MSOT work?
illuminates tissue with light pulses at multiple wavelengths and detects the acoustic waves generated by the thermoelastic expansion of the environment surrounding absorbing molecules.
What are acoustic waves?
Type of longitudinal waves that propagate by means of adiabatic compression and decompression.
What does adiabatic mean?
without transfer of heat or matter
what are acoustic waves ? and when are they used?
sound
longitudinal waves
for MSOT
What is the advantage of MSOT?
allows high-resolution imaging of photo-absorbers deep within tissue, beyond the classical depth and resolution limitations of conventional optical imaging.
What are gold nanoparticles?
Nanoparticles that exhibit strong optoacoustic responses due to plasmon resonance.
Why are gold nanoparticles not really clinically accepted in MSOT?
Long retention times in tissues.
but still provide good signal strength and photo-stability.
Why are gold nanoparticles still used?
They remain the current standard for signal generation in optoacoustic imaging due to their excellent signal strength and photo-stability.
what is indocyanine green (ICG)?
cyanide dye used in medical diagnostics
What does indocyanine green determine? uses
cardiac output
hepatic function
liver blood flow
ophthalmic angiography
What is the peak spectral absorption of ICG?
About 800 nm.
how does indocyanine green (ICG) work?
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
What happens to ICG once it binds to plasma proteins?
It becomes confined to the vascular system. :(
What is the half-life of ICG?
short
150 to 180 seconds.
How is ICG removed from circulation?
Exclusively by the liver to bile juice.
how are ICG administered?
encapsulated in a liposome
Solubility Of 5% Dextrose Solution Containing ICG In Water?
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
what is the advantage of encapsulating ICG? and what in?
LipoICG - in a liposome
acts as:
highly potent optoacoustic agent
high sensitivity and resolution to show vascularisation
What is ICG?
A fluorescent dye
used in imaging
What tumor model was used?
4T1 murine tumor model known for its fast growth
name a theranostic agent
Arginylglycylaspartic acid (RGD)
what is Arginylglycylaspartic acid (RGD)?
a theranostic agent
tripeptide composed of L- arginine, glycine and L-aspartic acid
What is the role of RGD-peptides?
Implicated in cellular attachment via integrins.
What is the MTT assay?
Assay to determine cytotoxicity.
Where do the SPIO nanocarriers accumulate primarily?
In the tumor and liver but not in most normal tissues.
Where do the SPIO nanocarriers accumulate primarily?
In the tumor and liver but not in most normal tissues.
Why are nanoparticles used in imaging and diagnostics?
Due to their intrinsic properties.
Encapsulation of existing fluorophores within soft or hard drug delivery systems can provide additional benefits, such as:
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
What are CLSM images?
Confocal laser scanning microscopy images.
To show U87MG cells treated with different nanocarriers and free DOX.
Tissue engineering…
what is the goal of tissue engineering?
replace/improve biological tissue and their functions
different tissue artificially made/formed into bone/vessels/bladder/muscle
What are the four factors of tissue engineering?
Scaffold.
Living cells/tissue.
Control over growth factors.
Culturing.
what is scaffolding in tissue engineering?
supporting tissue formation in 3D space
what does culturing include in tissue engineering?
maintain oxygen/pH/humidity/temp/nutrients/osmotic pressure
What are the basic principles of tissue engineering?
5 steps
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.
Seed the cultured cells on scaffolds in culture media supplemented with what?
growth factors
what kind of scaffolds will you need in the culture media?
those that recapture the extracellular matrix (ECM) and microenvironment to match where the injury site is
why do biomed nanomaterials play central role in tissue engineering?
as they may better support tissue regeneration
What are the 3 criteria for nanomaterials used as scaffold in tissue engineering?
Biocompatibility
Biodegradability
Low immunogenicity
What happens if incompatible biomaterials are used as scaffolds in tissue engineering?
Leads to an inflammatory response or foreign-body-reaction that eventually leads to rejection and/or necrosis.
smart biomaterial scaffold can maintain adequate mechanical integrity and simultaneously do what?
accelerate tissue formation during early stages of development
What does a scaffold made from nanoscaled fibres provide?
Good cellular interactions and tissue compatibility
What feature allows these nano materials to have good cellular interactions?
increased ratio of surface area to volume
improve mimicking of EC environment
What architectural properties contribute to tissue repair in terms of cell-material interactions?
porosity and surface features
biodegradability + biocompatibility are desirable to increase what?
success rate of implantation of a connstruct
biodegradability + biocompatibility are desirable to avoid what?
additional surgocal procedures and A SEs
biodegradability + biocompatibility are desirable but alos consider degradation of these materials why?
employed as additional infiltration path for cells/ as release mechanism for bioactive mols stored in scaffold
T/F
proper cell infiltration is vital
true
for cell migration, prolif, diff in scaffold
What should a good scaffold also do in tissue engineering?
Support cells.
Regulate the extracellular environment to enhance tissue alignment an cell-cell interactions.
what does a good scaffold lead to for the cell?
sufficient neovascularisation, adequate oxygen supply, and mechanism for waste disposal
without these, regenrated tissue will not function properly
selection of appropriate nanomaterial has significant impact on what?
functional tissue regeneration
advantages of metallic nanostrutures
optical adjustability
electrical conductivity
surface chemistry
ease of fabrication
Give an example of how metallic nanostructures are used clinically
engineered cardiac patches for treating damaged heart tissue after a heart attack.
what are engineered cardiac patches used for?
treating damaged heart tissues after a heart attack
how are engineered cardiac patches made? of
biological polymers - alginate /synthetic polymers
such as poly(lactic) acid (PLA)
what are engineered cardiac patches made of ?
metallic nanostructure
What limits cardiac patches made from metallic nanostructures from contracting strongly as a unit?
poor conductivity of the biological polymers used as scaffolds
Why might gold nanowires be used with alginate scaffolds?
enhances electrical communication and tissue thickness.
what does gold nanowires incorporated into alginate scaffolds show?
the cells in this tissue have shown the ability to contract synchronously corresponding to electrical stimuli
increased chance of contraction
name 3 materials used in metallic nano materials in tissue engineering?
gold, silver and titanium/Ti6Al4V
How are carbon nanotubes CNTs used in tissue engineering?
Cardiopulmonary applications as catheters.
neuronal tissue regeneration
Benefits of using carbon nanotubes in tissue engineering?
highly compatible with blood.
chemically inert.
neuronal tissue regeneration due to superior electrical conductivity = promote neurone attachment/growth /differentiation and long-term survival
what CNTs combines with to enhance its strength and elongation capacity?
polyurethane
what happens when CNTs are integrated into polyurethane?
enhance its strength and elongation capacity
anticoagulant properties
Why are cells encapsulated in tissue engineering?
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
Why are cells encapsulated in tissue engineering? 2
To overcome graft rejection.
Reduce need for long term immunosuppressants.
cell encapsulation: cells immobilised in polymeric semi-permeable membrane which permits what type of diffusion of mols such as influx of O2, nutrients, GF?
bidirectional
but semi perm membrane prevents immune cells and abtibodies destroying encapsulated cells
what are engineered cells encapsulated in?
polymeric semi-permeable membrane
when is collagen used in tissue engineering?
in the ECM
abundant mammal protein
to provide support to tissues - skin/cartilage/bones/blood vessels/ ligaments
Why is collagen a good model scaffold for tissue engineering?
Biocompatibility
Biodegradability
Ability to promote cell binding.
What properties facilitate printability for 3D bioprinting?
viscosity
gelation methods
rheological properties
what is biomimicry?
involves manufacture of identical reproductions of cellular and EC components of tissue/ organ
whats autonomous self assembly?
relies on cell as prim driver of histogenesis, directing composition, localisation, functionalisation, sstructural properties of tissue
example of a mini tissue?
kidney nephron
What must be considered in terms of biocompatibility in bioprinting?
materials should not induce local or systemic responses from host
What must be considered in terms of degradation in bioprinting?
degradation rates should match the cell’s ability to produce their own extracellular matrix
non-toxic
suitable swelling or contraction
Give examples of how bioprinting has been used on a human scale
skin
cartilage
aortic valves
how are cells regrown?
3D bioprinting has been used
