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CHEM426 > Inorganic Nanomedicines > Flashcards

Inorganic Nanomedicines Flashcards

1
Q

what are 2 properties of inorganic nanoparticles

A

between 1-100 nm

shows different properties to bulk

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2
Q

what 4 properties do inorganic nanoparticles have

A

optical
electrical
photothermal
magnetic

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3
Q

why are nanoparticles useful in medicine

A

not found natural in body so can be easily targeted

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4
Q

give 2 examples of treatments targeting nanoparticles

A

photothermal therapy

radio sensitisation enhancement

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5
Q

describe advantages of INPs in theranostics

A

large surface area can be tailored

can contain disease site targeting carriers

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6
Q

what are the 3 types of INPs

A

crystalline solids
composite materials
macromolecular metal ion chelates

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7
Q

give examples of crystalline solid INPs

A

colloidal gold

silver NPs

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8
Q

how are composite material nanoparticles made and give an example

A

dope nanoparticles with other metals

Au/Si nanoshells

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9
Q

what is the main barrier to market for most INPs

A

metal ion toxicity

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10
Q

why is metal ion toxicity a problem

A

excess ions overrun body
nanoparticles do not show same properties as bulk
distribution is difficult to study

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11
Q

how can metal ion toxicity be overcome

A

put metal in stable chelate or form stable nanoparticle

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12
Q

what conditions in the body must a nanomedicine withstand

A

37 degrees pH 7.4
local low pH
competing background media

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13
Q

what are the 2 main considerations when selecting ligands for a nanoparticle

A

HSAB

shape of particle

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14
Q

what are 3 processes that render a nanoparticle ineffective in vivo

A

electrolytes can cause aggregation of charge stabilised NPs
proteins can cause aggregation or form protein corona
can be opsonized

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15
Q

what is opsonization

A

marking for phagocytes

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16
Q

what are the 3 different types of metal nanoparticles

A

noble metals (Au/Ag)
oxides
binary NPs

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17
Q

what are the advantages of steric stabilisation of nanoparticles

A

stealthy to immune system using PEG groups

resistant to salts

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18
Q

what effects does size of hydrodynamic radii have

A 
small = better at avoiding opsonization
large = greater stability
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19
Q

what effect do macromolecular chelates have on metal ions

A

changes biodistribution
changes targeting
reduces off target toxicity

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20
Q

what must you bare in mind regarding macromolecular chelate stability

A

CFSE, CN

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21
Q

how can kinetic inertness be promoted

A

choose stable oxidation state

high CN

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22
Q

how are metallic inorganic nanoparticles synthesised

A

salt with salt solution
nucleate - reduce ion
grows until stable size is formed

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23
Q

what is the role of stabilisers in nanoparticle growth

A

stops aggregation

can also act as reducing agents

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24
Q

how can nanoparticles be made to be stable in aqueous solution

A

either; synthesise in aqueous

synthesise in organic do ligand exchange to aqueous

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25
Q

what are the 2 methods of targeting tumours

A

passive (EPR)

active - via overexpressed receptors in tumours

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26
Q

describe the properties of colloidal gold

A

stable, generally non toxic

surface plasmon resonance wavelength depends on NP size shape and surrounding medium

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27
Q

describe the Turkevich-Frens method

A

add citrate to HAuCl4
solution changes colour as gold is reduced
citrate is stabiliser and reducing agent
size controlled by Au citrate ratio

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28
Q

how is uniformity achieved in turkevich frens

A

pH 5 and uniform stirring

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29
Q

what size particles are formed in turkovich frens

A

10-15 nm

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30
Q

how can larger particles be made with turkovich frens

A

add HAuCl4 to citrate
forms seeds
further addition of Au grows particles

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31
Q

how can smaller particles be made using turkovich frens

A

add HAuCl4 to citrate
add NaBH4 - becomes main reducing agent
high citrate conc inhibits particle growth

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32
Q

describe the Brust-schriffrin method

A

HAuCl4 + tetraoctylammonium bromide + long chain thiol

forms stable nanoparticle 5-6 nm

33
Q

what determines ligand exchange on nanoparticle surfaces

A

ligands with higher affinity with displace others

34
Q

how can AuNP size be determined

A 
d = e^-B1 (Aspr / A450) - B2
B1 = 3
B2 = 2.2
35
Q

what size are SPIONs and what are they stabilised by

A

5-50nm

stabilised by carbohydrates

36
Q

what are the key points about superparamagnetism

A

particle must be small <50 nm

must only have 1 domain

37
Q

what are the 4 methods of SPION synthesis

A

Coprecipitation
thermal decomposition
micro emulsion
sol gel

38
Q

describe the co-precipitation method of SPION formation

A

mix of Fe2+/Fe3+ warmed with base and carbohydrate stabilisers

39
Q

what are size and shape influenced by in coprecipitation

A

Fe2+/Fe3+ ratio
Temp and pH
counter ion
Base

40
Q

what are the pros and cons of co precipitation

A

simple

hard to control size and shape

41
Q

describe the process of thermal decompositon

A

Fe3+ oleate is used as precursor

olelic acid is used as stabiliser

42
Q

what is size determined by in thermal decomposition

A

rate of temp increase

can be finely tuned

43
Q

what is a drawback of thermal decomposition

A

needs toxic chemicals

44
Q

describe the process of microemulsion

A

form oil in water with surfactant in oil and Fe2+/3+ in water

45
Q

what are the advantages and disadvantages of microemulsion

A

high control over size and shape

lower yield as done at low temp

46
Q

describe sol gel spion synthesis

A

Fe3+ soln + ethanol + h2o2 + TEOS forms gel and iron oxide structure crushed to form nanoparticles

47
Q

what are the advantages and disadvantages of sol gel

A

can form large particles

need purification from byproducts

48
Q

how can spions be characterised

A 
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
49
Q

what can SQUID be used to measure

A

remanance and coercivity

50
Q

what is coercivity

A

the reverse field need to reduce magnetisation to 0

51
Q

what is remanance

A

magnetisation when applied field is removed

52
Q

what should coercivity and remanance equal in spions

A

0

53
Q

what can dynamic light scatterring determine about a spion

A

hydrodynamic radius

54
Q

what can TEM determine about a SPION

A

particle size

55
Q

how is an MRI signal generated

A

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

56
Q

what are the 2 types of proton relaxation

A

T1 and T2

57
Q

describe T1 relaxation

A

Mz grows over time
depends on physical and chemical environment
shorter T1 lead to brighter MRI

58
Q

describe T2 relaxation

A

depends on local static magnetic environment

shorter T2 = darker image

59
Q

how does the length of T1 relaxation compare to T2

A

T2 is shorter than T1

60
Q

how can T1 or T2 be increased

A

using contrast agents

61
Q

what are the advantages of MRI

A 
non invasive
non ionising
good soft tissue contrast
high resolution
produced 3D whole body images
62
Q

what are the disadvantages of MRI

A

poor sensitivity

- needs many scans to overcome noise - takes time

63
Q

what is a typical T1 contrast agent

A

Gd(III)

64
Q

what is a typical T2 contrast agent

A

SPION

65
Q

what are the main factors affecting relaxivity

A

number of bound waters
water exchange lifetime
molar conc
rotational correlation time

66
Q

how does Gd(III) affect tumbling

A

reduces tumbling leading to brighter NMR

67
Q

how are Gd(III) complexes designed as contrast agents

A

8 coordinate allows for binding of water

must be kinetically inert

68
Q

how are Gd(III) ions usually administered and why

A

demidrimer with conjugated Gd(III) chelates
allows for many Gd(III) in one compound
has longer circulation time

69
Q

what is an alternative way of Gd(III) administration

A

polymer conjugated Gd(III) chelates

assemble into micelles and fibres

70
Q

how do Gd(III) micelles and fibre compare

A

micelles have better retention

fibres have better relaxation

71
Q

what is a dual effect method of Gd(III) administration

A

liposome Gd(III) chelates can also contain drugs (doxorubicin)

72
Q

what are potential advantages of spion contrast agents

A

high sensitivity and low toxicity
wide range of functionalisation possible
greater magnetisation

73
Q

why will spions be even more useful in the future

A

increased magnetic strength favours spions

74
Q

what is outer sphere relaxation determined by

A

T2

75
Q

what is the formula for total relaxation

A

outer sphere + inner sphere

76
Q

how can spions used with regard to lymph nodes

A

microphages collect in lymphs can be tracked if they do not accumulate lymphs are unhealthy

77
Q

how can spions be used for tracking

A

are consumed by phagocytes

78
Q

how can spions be used to learn about illness

A

label stem cells
inject them
track where they go

CHEM426 (4 decks)

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