Nanotoxicology Flashcards
what is toxicology?
science of poisons
study of AEs of chemical substances on living organisms
=> assesses probability of hazards caused by such effects
name examples of diverse new material in nanorange
eg soft and hard NPs
(liposomes, dendrimers, gold NPs, quantum dots, CNTs, fullerenes….)
T/F nanomeds have diff properties from their bulk materials?
true
size
surface charge
shape
aspect ratio
stability/ agglomeration
what do the properties of nanomeds impact?
biological activity: unique, and behaviour inside body
cellular uptake, biodistribution, toxicokinetics
why is nanoparticle size important for nanotoxicology?
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
why is nanoparticle surface charge important for nanotoxicology?
increase conc of [DOPC:DOTAP:CHOL] in DOPC:DOTAP:CHOL:PEG liposomes
DOPC:DOTAP:CHOL = positive charge
charged liposomes = cleared quickly
are charged liposomes cleared quicker/ slower from bloodstream than non-charged?
quicker
incorporating 6% mol of
PEG750 and PEG5000 into PC:Chol liposomes would increase/ decrease half life?
increase blood circ t1/2
what does DOPC:DOTAP:CHOL do to liposomes?
give it a/increase positive charge = aggregate with proteins in the blood = lung accumulation
where do DOPC:DOTAP:CHOL liposomes deliver drugs? why?
lung
due to protein aggregation due to their positive charge
how does PEG increase t1/2 in nanotoxicology?
mask surface charge = stop lung accumulation and fast excretion
= increasing the liposomes half life
why is nanoparticle shape important for nanotoxicology?
phagocytosis
pointed end of elliptical disc = fast phagocytosis (few minutes)
contact with flat region = slow phagocytosis (over 12hours)
what of the nanoparticle at first contact with macrophages is the determinant factor in phagocytosis?
geometry
at what stages of pahgocytosis is NP size important?
later
is it just 1 factor, or synergistic effects between the characteristics of NP that affect its tox?
synergistic effects
charge
size
shape
chemical composition
solubility
aggregation
dispersion
why is it hard to use traditional toxicology assays for NPs?
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
what are traditional toxicology assays?
MTT - mitochondrial succinate dehydrogenase
LDH- lactate dehydrogenase
what reagents are used in traditional toxicology assays?
polycyclic nature/rings
how does LDH- lactate dehydrogenase work?
LDH releases when cells have defects in the membrane
= LDH detection
= toxicology reported
MTT used to see what about cell?
how viable it is
what is the toxic effect of NPs we are worried about?
biological side effects
environmental/workplace exposure of CNTs - lung and skin exposure
2 main areas of nanotoc?
clinical
environmental
name NP affects
(everything and increases with dose and duration)
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
what type of NPs are less toxic?
chemically functionalised CNTs
everything is toxic… just a matter of (3)
dose
duration
frequency
.. so cant generalise bc of diversity of NPs, even in same class
pristine CNTs are very hydrophobic/philic
hydrophobic
pristine CNTs are very hydrophobic/philic
hydrophobic
short or tangles MWNT (<5-10um) will be:
- cleared through lymphatic system :)
- or mutagenesis caused by MWNT accumulator -> cancer
cleared through lymphatic system :)
short or tangles MWNT (<5-10um) will be:
- cleared through lymphatic system :)
- or mutagenesis caused by MWNT accumulator -> cancer
cleared through lymphatic system :)
what type of chemical functionalisations can you make to MWNTs?
- addition of alkyl chain - hydrophobic
- addition of ammonium chain - hydrophobic, increase dispersibility
how are inflammatory reactions noticed with CNTs?
granuloma formation
- mass of immune cells that forms when the immune system attempts to eliminate substances seen as foreign but cant eliminate them
whats the difference between NT2 pristine and NT2 alykl/TEG?
NT2 alkyl and NT2 TEG had lower amounts of granulation than NT2 pristine
why does NT2 alkyl and NT2 TEG have lower amounts of granulation than NT2 pristine?
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
chemical functionalisation can remove carcinogenic risk associated with…
long chain MWNT
smaller CNTs better?
yes
how are CNTs degraded?
horseradish peroxidase (HRP) enzyme with low conc.
hydrogen peroxide
myeloperoxidases (MPO)
what can horseradish peroxidase (HRP) enzyme with low conc. hydrogen peroxide be used for?
degrading CNTs - SWCNT and MWCNTs
what is myeloperoxidases (MPO) used for ?
CNT degradation
what is hMPO used for ?
implantable polymer degradation
pristine CNTs failed to be degraded T/F?
true
importance of defected sites (carboxylated CNT + ammonium functionalised CNT)
cellular CNT biodegradation
- in isolated human phagocytes for engulfed CNTs.
CNT degradation in vivo =
lung + brain inside resident/ recruited macrophages for engulfed CNTs (local admin)
general safety rules with CNTs (3)
- 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
