Inorganic Nanomedicines Flashcards by willl ackerman

what are 2 properties of inorganic nanoparticles

between 1-100 nm

shows different properties to bulk

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what 4 properties do inorganic nanoparticles have

optical
electrical
photothermal
magnetic

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why are nanoparticles useful in medicine

not found natural in body so can be easily targeted

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give 2 examples of treatments targeting nanoparticles

photothermal therapy

radio sensitisation enhancement

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describe advantages of INPs in theranostics

large surface area can be tailored

can contain disease site targeting carriers

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what are the 3 types of INPs

crystalline solids
composite materials
macromolecular metal ion chelates

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give examples of crystalline solid INPs

colloidal gold

silver NPs

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how are composite material nanoparticles made and give an example

dope nanoparticles with other metals

Au/Si nanoshells

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what is the main barrier to market for most INPs

metal ion toxicity

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why is metal ion toxicity a problem

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

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how can metal ion toxicity be overcome

put metal in stable chelate or form stable nanoparticle

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what conditions in the body must a nanomedicine withstand

37 degrees pH 7.4
local low pH
competing background media

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

HSAB

shape of particle

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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

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what is opsonization

marking for phagocytes

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what are the 3 different types of metal nanoparticles

noble metals (Au/Ag)
oxides
binary NPs

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what are the advantages of steric stabilisation of nanoparticles

stealthy to immune system using PEG groups

resistant to salts

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what effects does size of hydrodynamic radii have

small = better at avoiding opsonization
large = greater stability

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what effect do macromolecular chelates have on metal ions

changes biodistribution
changes targeting
reduces off target toxicity

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what must you bare in mind regarding macromolecular chelate stability

CFSE, CN

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how can kinetic inertness be promoted

choose stable oxidation state

high CN

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how are metallic inorganic nanoparticles synthesised

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

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what is the role of stabilisers in nanoparticle growth

stops aggregation

can also act as reducing agents

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how can nanoparticles be made to be stable in aqueous solution

either; synthesise in aqueous

synthesise in organic do ligand exchange to aqueous

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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

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

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

Inorganic Nanomedicines Flashcards

(78 cards)