3. Toxicology Flashcards
Give examples of materials which have different properties at the nanoscale.
Gold is yellow, while gold nanoparticles in solution have a colour ranging from red to purple. TiO2 is white while TiO2 NPs are transparent. The melting temperature of Ag is much lower than of bulk Ag.
Why do nanomaterials generally have a higher reactivity than bulk materials?
the surface area per mass is much larger than for bulk material, and consequently number of surface molecules increases (exponentially with reduced particle size).
Describe ways of accidental and deliberate exposure to NPs.
accidental: occupational exposure, consumer exposure, and environmental exposure (waste). deliberate: medical / pharmaceutical applications (oral, topical, via injection).
What happens when a NP enters the bloodstream?
serum proteins and opsonins (IgG and complement factors) bind to NP opsonisation results in transfer of NP to spleen and liver (mononuclear phagocyte system)
How can you design a NP with reduced clearance by opsonisation?
PEG coating.
What happens with a NP after inhalation?
disposition in a part of the respiratory tract, interaction with lung fliud/surfactant, clearance (physical dislocation or chemical clearance)
What happens with a NP after oral exposure
passes GI tract. no intestinal absorption
In which circumstances do you get systemic toxicity , after dermal exposure?
When the NP crosses the epidermis and reaches the dermis which has blood vessels.
What happens with a NP after absorption, and biodistribution occurs?
Interaction with plasma proteins (corona formation), with the immune system, with blood cells, and distribution to organs where it may interact with cells.
Describe what a protein corona is and how it evolves over time.
3 types of proteins (green, blue and yellow :)). soft corona and hard corona (several days) composition is determined by NP properties and by biological milieu. influential role biological fate: cellular uptake (endocytosis), biodistribution, toxicity
Describe the intracellular fate and biotransformation
xx
How are NPs generally eliminated?
endosomal/lysosomal degradation, phagocytocis.
Which signs can you expect when NPs accumulate in the body?
frustrated phagocystosis and inflammation
Describe 6 mechanisms of NP toxicity
disruption of the cell membrane, disruption of transport processes, altered protein folding, protein aggregation, ROS, dissolution and release of toxic ions.
How can NPs result in the generation of reactive oxygen species?
- on NP surface: compounds which release ROS (pro-oxidant functioncal groups), or metal ions or quinones on the NP surface which catalyse OH radical or O2-radical formation. - in the cell, interaction with redox processes: membrane NADHP enzyme interaction, mitochondria interaction, ER interaction.