Bionanotechnology Strategies for Cell Detection - Bionanotechnology: Global Prospects - page 30

QDs.. It. was. shown. that. the. cellular. viability. decreased. at. higher. QD. concentrations,. in.
which.most.of.the.cells.died.after.6.h..A.high.rate.of.cellular.death.has.also.been.observed.
in.adipose.tissue-derived.stem.cells.transfected.with.more.than.2.0.nM.QD655. 119 .Injection.
of.5.×.10 9 .QDs/cell.into.xenopus.blastomeres.resulted.in.various.abnormalities.in.embryos,.
such. as. changes. in. cell. size,. cell. movement,. axis. elongation,. and. posterior. truncations,.
while.embryos.injected.with.2.×.10 9 .QDs/cell.were.statically.similar.to.uninjected.embry-
os. 74 .High.levels.of.malformations.and.embryonic.death.have.also.been.found.in.zebra.ish.
embryos.injected.with.excessive.QDs. 110 .Live.embryos.are.ideal.models.for.investigating.
toxic.effects.due.to.the.extreme.sensitivity.to.even.slight.perturbations,.which.generally.
results. in. phenotype. abnormalities. 83 . Dose-dependent. cytotoxic. effects. suggest. that. for.
continuous. in. vivo. monitoring. of. transplanted. cells,. QD. exposure. should. be. limited. to.
minimally.low.concentrations. 165
The.consensus.of.many.studies.for.in.vitro.and.in.vivo.toxicity.is.that.encapsulation.of.
QDs.within.a.stable.shell.has.been.shown.to.predominantly.reduce.toxicity.by.providing.
a.physical.barrier.against.degradation.or.oxidation.of.the.nanoparticles..In.human.breast.
cancer. MCF-7. cells,. bare. CdTe. results. in. cellular. alteration,. while. coating. with. different.
capping. materials,. such. as. mercaptopropionic. acid,. cysteamine,. and. n-acetylcysteine,.
decreased.the.relative.toxicity.for.the.time.periods.studied. 166,167 .However,.the.toxicity.of.the.
capping.materials.should.also.be.considered,.since.several.groups.have.found.increased.
cytotoxicity.associated.with.capping.materials.such.as.mercaptoacetic.acid.(MAA). 168
The.stability.of.QDs.under.certain.conditions.is.anticipated.as.the.most.important.aspect.
of.their.cell-induced.toxicity..Despite.many.modiications.for.increasing.nanoparticle.sta-
bility,.several.studies.suggested.that.under.oxidative.and.photolytic.conditions,.QDs.are.
labile. and. thus. are. subjected. to. degradation. 27 . In. addition,. the. long. nanoparticle. persis-
tence.inside.living.animals,.which.results.in.their.subsequent.degradation.over.time,.also.
requires.more.consideration.for.improving.their.pharmacokinetics.and.accelerating.their.
biotransformation.and.removal..The.large.hydrodynamic.size.of.QDs,.small.pore.sizes.in.
the.mammalian.vasculature,.and.the.glomerular.barrier.are.the.limiting.factors.in.the.nano-
particles'.body.clearance..By.choosing.appropriate.surface.coatings.and.optimal.hydrody-
namic.diameters, 169,170 .we.can.effectively.clear.most.of.the.QDs.from.the.organism. 76
At.least.four.possible.mechanisms.have.been.assumed.to.be.responsible.for.the.toxicity.
induced.by.QDs.in.living.cells:.(1).liberation.of.toxic.components.of.the.core, 160,171,172 .(2).gen-
eration.of.free.radicals,.particularly.reactive.oxygen.species.(ROS), 159,162,173 .(3).interaction.of.
QDs.with.intracellular.components, 27 .and.(4).nanoparticle.aggregation.and.precipitation.
on. the. cellular. surface. 160 . The. exact. recognition. of. the. speciic. mechanisms. involved. in.
QD-induced.cellular.toxicity.is.highly.crucial.before.any.clinical.translation.
Regarding. the. high. cytotoxic. potential. of. divalent. cations,. their. liberation. from. the.
nanoparticle's.core.following.photodegradation,.air.oxidation,.or.intracellular.decomposi-
tion.is.of.serious.concern..In.order.to.evaluate.the.toxicity.induced.by.free.Cd 2+ ,.rat.primary.
hepatocytes. used. as. a. liver. model. were. cultured. in. bare. CdSe. QD. solution. and. subse-
quently. exposed. to. ultraviolet. light. (UV). or. air.. It. was. suggested. that. the. nanoparticle.
surface.oxidation,.either.air.induced.or.UV.catalyzed,.was.responsible.for.free.cadmium.
level. elevation, 61,174 . and. a. direct. correlation. existed. between. Cd 2+ . concentration. and. the.
extent.of.hepato-toxicity..However,.it.was.only.assumed.that.the.underlying.mechanism.of.
cytotoxicity.was.the.inactivation.of.essential.mitochondrial.proteins.through.interaction.
between.free.cadmium.and.the.sulfhydryl.group 175 ;.thiol.group.inactivation.then.resulted.
in.oxidative.stress.and.mitochondrial.dysfunction..Metallothionein,.a.protein.found.in.the.
cytoplasm. of. hepatocytes,. detoxiies. cadmium. by. sequestering. it. into. an. inert. complex..