Nanotoxicology Flashcards

1
Q

what is toxicology?

A

science of poisons
study of AEs of chemical substances on living organisms

=> assesses probability of hazards caused by such effects

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2
Q

name examples of diverse new material in nanorange

A

eg soft and hard NPs
(liposomes, dendrimers, gold NPs, quantum dots, CNTs, fullerenes….)

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3
Q

T/F nanomeds have diff properties from their bulk materials?

A

true

size
surface charge
shape
aspect ratio
stability/ agglomeration

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4
Q

what do the properties of nanomeds impact?

A

biological activity: unique, and behaviour inside body

cellular uptake, biodistribution, toxicokinetics

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5
Q

why is nanoparticle size important for nanotoxicology?

A

diameter dependent excretion
e.g. zwitterionic cysteine coated quantum dots
e.g. PMAM-gold NPs accumulate in the blood = increase size

larger size found in liver and spleen
smaller size excreted in the urine

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6
Q

why is nanoparticle surface charge important for nanotoxicology?

A

increase conc of [DOPC:DOTAP:CHOL] in DOPC:DOTAP:CHOL:PEG liposomes

DOPC:DOTAP:CHOL = positive charge

charged liposomes = cleared quickly

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7
Q

are charged liposomes cleared quicker/ slower from bloodstream than non-charged?

A

quicker

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8
Q

incorporating 6% mol of
PEG750 and PEG5000 into PC:Chol liposomes would increase/ decrease half life?

A

increase blood circ t1/2

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9
Q

what does DOPC:DOTAP:CHOL do to liposomes?

A

give it a/increase positive charge = aggregate with proteins in the blood = lung accumulation

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10
Q

where do DOPC:DOTAP:CHOL liposomes deliver drugs? why?

A

lung
due to protein aggregation due to their positive charge

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11
Q

how does PEG increase t1/2 in nanotoxicology?

A

mask surface charge = stop lung accumulation and fast excretion
= increasing the liposomes half life

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12
Q

why is nanoparticle shape important for nanotoxicology?

A

phagocytosis

pointed end of elliptical disc = fast phagocytosis (few minutes)
contact with flat region = slow phagocytosis (over 12hours)

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13
Q

what of the nanoparticle at first contact with macrophages is the determinant factor in phagocytosis?

A

geometry

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14
Q

at what stages of pahgocytosis is NP size important?

A

later

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15
Q

is it just 1 factor, or synergistic effects between the characteristics of NP that affect its tox?

A

synergistic effects
charge
size
shape
chemical composition
solubility
aggregation
dispersion

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16
Q

why is it hard to use traditional toxicology assays for NPs?

A

e.g. CNTs - π–π stacking between CNT and reagents in the toxicology assays like MTT and LDH assay

π–π stacking with polycyclic nature/rings = blocks absorbance and fluorescent readings

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17
Q

what are traditional toxicology assays?

A

MTT - mitochondrial succinate dehydrogenase
LDH- lactate dehydrogenase

18
Q

what reagents are used in traditional toxicology assays?

A

polycyclic nature/rings

19
Q

how does LDH- lactate dehydrogenase work?

A

LDH releases when cells have defects in the membrane
= LDH detection
= toxicology reported

20
Q

MTT used to see what about cell?

A

how viable it is

21
Q

what is the toxic effect of NPs we are worried about?

A

biological side effects
environmental/workplace exposure of CNTs - lung and skin exposure

22
Q

2 main areas of nanotoc?

A

clinical
environmental

23
Q

name NP affects
(everything and increases with dose and duration)

A

NP inhalation
- brain - parkinson’s/alzheimer’s
- lung - asthma/bronchitis/emphysema/cancer
- circulatory - artherosclerosis/ vasoconstriction/ thrombus/ high bP
- heart - arrhythmia/ heart disease/ death
- lymphatic system - kaposi’s sarcoma
- skin - auto-immune diseases

NP ingestion
- GI - crohn’s disease/colon cancer
- orthopedic implants wear debris - auto-immune diseases/dermatitis/ urticaria/vasculitis

24
Q

what type of NPs are less toxic?

A

chemically functionalised CNTs

25
Q

everything is toxic… just a matter of (3)

A

dose
duration
frequency

.. so cant generalise bc of diversity of NPs, even in same class

26
Q

pristine CNTs are very hydrophobic/philic

A

hydrophobic

27
Q

pristine CNTs are very hydrophobic/philic

A

hydrophobic

28
Q

short or tangles MWNT (<5-10um) will be:
- cleared through lymphatic system :)
- or mutagenesis caused by MWNT accumulator -> cancer

A

cleared through lymphatic system :)

28
Q

short or tangles MWNT (<5-10um) will be:
- cleared through lymphatic system :)
- or mutagenesis caused by MWNT accumulator -> cancer

A

cleared through lymphatic system :)

29
Q

what type of chemical functionalisations can you make to MWNTs?

A
  1. addition of alkyl chain - hydrophobic
  2. addition of ammonium chain - hydrophobic, increase dispersibility
30
Q

how are inflammatory reactions noticed with CNTs?

A

granuloma formation
- mass of immune cells that forms when the immune system attempts to eliminate substances seen as foreign but cant eliminate them

31
Q

whats the difference between NT2 pristine and NT2 alykl/TEG?

A

NT2 alkyl and NT2 TEG had lower amounts of granulation than NT2 pristine

32
Q

why does NT2 alkyl and NT2 TEG have lower amounts of granulation than NT2 pristine?

A

NT2 pristine- after sonication still forms long and hydrophobic needles
NT2 alkyl and NT2 TEG- after sonication forms smaller CNTs easier to be phagocytosed by the cell

33
Q

chemical functionalisation can remove carcinogenic risk associated with…

A

long chain MWNT

34
Q

smaller CNTs better?

A

yes

35
Q

how are CNTs degraded?

A

horseradish peroxidase (HRP) enzyme with low conc.

hydrogen peroxide
myeloperoxidases (MPO)

36
Q

what can horseradish peroxidase (HRP) enzyme with low conc. hydrogen peroxide be used for?

A

degrading CNTs - SWCNT and MWCNTs

37
Q

what is myeloperoxidases (MPO) used for ?

A

CNT degradation

38
Q

what is hMPO used for ?

A

implantable polymer degradation

39
Q

pristine CNTs failed to be degraded T/F?

A

true

importance of defected sites (carboxylated CNT + ammonium functionalised CNT)

40
Q

cellular CNT biodegradation

  • in isolated human phagocytes for engulfed CNTs.
    CNT degradation in vivo =
A

lung + brain inside resident/ recruited macrophages for engulfed CNTs (local admin)

41
Q

general safety rules with CNTs (3)

A
  • avoid large/ long and wide structures
    smaller than 5-10um and 20nm diameter good
  • get decent surface hydrophilicity
  • avoid accumulation in tissues: higher degree of CNT individualisation in vivo = higher urinary excretion.
    use small single well dispersed sheets of graphene