Inorganic Nanomedicines Flashcards
what are 2 properties of inorganic nanoparticles
between 1-100 nm
shows different properties to bulk
what 4 properties do inorganic nanoparticles have
optical
electrical
photothermal
magnetic
why are nanoparticles useful in medicine
not found natural in body so can be easily targeted
give 2 examples of treatments targeting nanoparticles
photothermal therapy
radio sensitisation enhancement
describe advantages of INPs in theranostics
large surface area can be tailored
can contain disease site targeting carriers
what are the 3 types of INPs
crystalline solids
composite materials
macromolecular metal ion chelates
give examples of crystalline solid INPs
colloidal gold
silver NPs
how are composite material nanoparticles made and give an example
dope nanoparticles with other metals
Au/Si nanoshells
what is the main barrier to market for most INPs
metal ion toxicity
why is metal ion toxicity a problem
excess ions overrun body
nanoparticles do not show same properties as bulk
distribution is difficult to study
how can metal ion toxicity be overcome
put metal in stable chelate or form stable nanoparticle
what conditions in the body must a nanomedicine withstand
37 degrees pH 7.4
local low pH
competing background media
what are the 2 main considerations when selecting ligands for a nanoparticle
HSAB
shape of particle
what are 3 processes that render a nanoparticle ineffective in vivo
electrolytes can cause aggregation of charge stabilised NPs
proteins can cause aggregation or form protein corona
can be opsonized
what is opsonization
marking for phagocytes
what are the 3 different types of metal nanoparticles
noble metals (Au/Ag)
oxides
binary NPs
what are the advantages of steric stabilisation of nanoparticles
stealthy to immune system using PEG groups
resistant to salts
what effects does size of hydrodynamic radii have
small = better at avoiding opsonization large = greater stability
what effect do macromolecular chelates have on metal ions
changes biodistribution
changes targeting
reduces off target toxicity
what must you bare in mind regarding macromolecular chelate stability
CFSE, CN
how can kinetic inertness be promoted
choose stable oxidation state
high CN
how are metallic inorganic nanoparticles synthesised
salt with salt solution
nucleate - reduce ion
grows until stable size is formed
what is the role of stabilisers in nanoparticle growth
stops aggregation
can also act as reducing agents
how can nanoparticles be made to be stable in aqueous solution
either; synthesise in aqueous
synthesise in organic do ligand exchange to aqueous
what are the 2 methods of targeting tumours
passive (EPR)
active - via overexpressed receptors in tumours
describe the properties of colloidal gold
stable, generally non toxic
surface plasmon resonance wavelength depends on NP size shape and surrounding medium
describe the Turkevich-Frens method
add citrate to HAuCl4
solution changes colour as gold is reduced
citrate is stabiliser and reducing agent
size controlled by Au citrate ratio
how is uniformity achieved in turkevich frens
pH 5 and uniform stirring
what size particles are formed in turkovich frens
10-15 nm
how can larger particles be made with turkovich frens
add HAuCl4 to citrate
forms seeds
further addition of Au grows particles
how can smaller particles be made using turkovich frens
add HAuCl4 to citrate
add NaBH4 - becomes main reducing agent
high citrate conc inhibits particle growth
describe the Brust-schriffrin method
HAuCl4 + tetraoctylammonium bromide + long chain thiol
forms stable nanoparticle 5-6 nm
what determines ligand exchange on nanoparticle surfaces
ligands with higher affinity with displace others
how can AuNP size be determined
d = e^-B1 (Aspr / A450) - B2 B1 = 3 B2 = 2.2
what size are SPIONs and what are they stabilised by
5-50nm
stabilised by carbohydrates
what are the key points about superparamagnetism
particle must be small <50 nm
must only have 1 domain
what are the 4 methods of SPION synthesis
Coprecipitation
thermal decomposition
micro emulsion
sol gel
describe the co-precipitation method of SPION formation
mix of Fe2+/Fe3+ warmed with base and carbohydrate stabilisers
what are size and shape influenced by in coprecipitation
Fe2+/Fe3+ ratio
Temp and pH
counter ion
Base
what are the pros and cons of co precipitation
simple
hard to control size and shape
describe the process of thermal decompositon
Fe3+ oleate is used as precursor
olelic acid is used as stabiliser
what is size determined by in thermal decomposition
rate of temp increase
can be finely tuned
what is a drawback of thermal decomposition
needs toxic chemicals
describe the process of microemulsion
form oil in water with surfactant in oil and Fe2+/3+ in water
what are the advantages and disadvantages of microemulsion
high control over size and shape
lower yield as done at low temp
describe sol gel spion synthesis
Fe3+ soln + ethanol + h2o2 + TEOS forms gel and iron oxide structure crushed to form nanoparticles
what are the advantages and disadvantages of sol gel
can form large particles
need purification from byproducts
how can spions be characterised
XRD can detect the iron oxide structure tau = klambda/bcos(theta) tau = domain size k = shape factor (0.9) lambda = x-ray wavelength B = line broadening theta = diffraction angle
what can SQUID be used to measure
remanance and coercivity
what is coercivity
the reverse field need to reduce magnetisation to 0
what is remanance
magnetisation when applied field is removed
what should coercivity and remanance equal in spions
0
what can dynamic light scatterring determine about a spion
hydrodynamic radius
what can TEM determine about a SPION
particle size
how is an MRI signal generated
when magnetic field is applied proton spins align with or against field
90 degree RF pulse brings vector to xy plane
when RF pulse is released vector relaxes
what are the 2 types of proton relaxation
T1 and T2
describe T1 relaxation
Mz grows over time
depends on physical and chemical environment
shorter T1 lead to brighter MRI
describe T2 relaxation
depends on local static magnetic environment
shorter T2 = darker image
how does the length of T1 relaxation compare to T2
T2 is shorter than T1
how can T1 or T2 be increased
using contrast agents
what are the advantages of MRI
non invasive non ionising good soft tissue contrast high resolution produced 3D whole body images
what are the disadvantages of MRI
poor sensitivity
- needs many scans to overcome noise - takes time
what is a typical T1 contrast agent
Gd(III)
what is a typical T2 contrast agent
SPION
what are the main factors affecting relaxivity
number of bound waters
water exchange lifetime
molar conc
rotational correlation time
how does Gd(III) affect tumbling
reduces tumbling leading to brighter NMR
how are Gd(III) complexes designed as contrast agents
8 coordinate allows for binding of water
must be kinetically inert
how are Gd(III) ions usually administered and why
demidrimer with conjugated Gd(III) chelates
allows for many Gd(III) in one compound
has longer circulation time
what is an alternative way of Gd(III) administration
polymer conjugated Gd(III) chelates
assemble into micelles and fibres
how do Gd(III) micelles and fibre compare
micelles have better retention
fibres have better relaxation
what is a dual effect method of Gd(III) administration
liposome Gd(III) chelates can also contain drugs (doxorubicin)
what are potential advantages of spion contrast agents
high sensitivity and low toxicity
wide range of functionalisation possible
greater magnetisation
why will spions be even more useful in the future
increased magnetic strength favours spions
what is outer sphere relaxation determined by
T2
what is the formula for total relaxation
outer sphere + inner sphere
how can spions used with regard to lymph nodes
microphages collect in lymphs can be tracked if they do not accumulate lymphs are unhealthy
how can spions be used for tracking
are consumed by phagocytes
how can spions be used to learn about illness
label stem cells
inject them
track where they go
