Biomedical Engineering Reference
In-Depth Information
applications,.such.as.drug.and.gene.delivery,.bioseparation,.and.biological.detection..The.
area.of.multimodality.molecular.imaging.is.moving.from.a.research.curiosity.to.one.hav-
ing.preclinical.and.clinical.applications.
2.14 Cytotoxicity
With.the.wide-ranging.use.of.QDs.for.bioimaging.and.in.vivo.animal.imaging.there.have.
been. increasing. concerns. over. their. short-. and. long-term. toxicity,
156
. which. could. be. one.
of.the.important.restricting.factors.for.their.use.as.potential.bioprobes.in.future.clinical.
applications.
27
.For.the.purpose.of.introducing.this.technology.in.a.clinical.setting,.numer-
ous. in. vitro. and. in. vivo. animal-based. assays. have. been. focused. on. preclinical. testing..
However,. presently,. it. is. dificult. to. make. a. irm. conclusion. about. the. toxic. potential. of.
these.nanoparticles,.due.to.the.contradictory.results.found.in.current.literature,
157
.which.
could. be. attributed. to. the. lack. of. any. standardized. synthesis. protocol,. surface. coating,.
solubilization.ligands,.dose,.exposure.time,.and.inally,.the.studied.cell.system.
158
.Several.
factors. are. generally. involved. in. QD. cytotoxicity,. as. with. other. nanoparticles,. that. are.
associated.with.inherent.particles'.physiochemistry.as.well.as.the.external.environmental.
conditions.. The. toxicity. induced. by. physiochemical. properties. of. a. particular. QD. origi-
nates.from.its.overall.size,.electrical.charge,.concentration,.surface.coating,.and.oxidative,.
photolytic,. and. mechanical. stability,. all. of. which. should. be. considered. individually. for.
toxicological.assessment.
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There.are.several.studies.that.conirmed.the.relative.dependency.between.particle.size.
and. the. resulting. toxicity. at. both. the. intracellular. and. animal. levels.. The. initial. study.
presented.by.Lovric.et.al..demonstrated.that.2.2.nm.CdTe.QDs,.compared.to.the.5.2.nm.
ones,.led.to.higher.cellular.death,.which.could.be.related.to.the.different.subcellular.dis-
tribution,.as.larger.nanoparticles.have.been.found.distributed.inside.the.cytoplasm,.with.
none.entering.the.nucleus,.while.smaller.particles.have.been.mainly.localized.within.the.
nuclear. compartments.. The. interaction. between. QDs. and. nuclear. DNA. or. proteins. has.
been.found.to.induce.different.types.of.genotoxicity.
157,159
.In.another.study.by.Kirchner.and.
co-workers. different. cell. lines,. including. NRK. ibroblasts,. MDA-MB-435S. breast. cancer.
cells,.CHO.cells,.and.RBL.cells,.were.exposed.to.the.same.concentration.of.CdSe-ZnS.QDs..
It.was.suggested.that.the.higher.surface-to-volume.ratio.in.smaller.particles.is.responsible.
for.their.greater.cytotoxic.effects.
160
The.surface.charge.is.also.a.key.factor.for.particle.dispersion.and.the.behavior.of.par-
ticles. in. living. organisms.. For. evaluating. the. toxicity. related. to. surface. charge. in. hepa-
tocytes,. Hoshino. et. al.
161
. coated. CdSe-ZnS. QDs. with. mercaptoundecanoic. acid. (MUA).
(QD-COOH),.cysteamine.(QD-NH2),.and.thioglycerol.(QD-OH),.as.well.as.their.combina-
tions.
162
.The.results.revealed.that.the.toxicity.depends.on.the.type.of.ligand.used.for.surface.
modiication,.but.not.on.the.core.material;.the.highly.negative.charge.in.MUA-coated.QDs.
induced.DNA.damage.after.2.h,.while.thioglycerol.with.a.lower.negative.charge.had.the.
least. genotoxicity. and. therefore. cellular. damage.. In. another. study,. neutral. polyethylene.
glycol. (PEG)-coated. QDs. were. found. to. be. less. toxic. in. human. epidermal. keratinocytes.
(HEKs),in.an.established.in.vitro.model.for.epidermal.toxicity,.when.compared.to.cationic.
PEG-amine.or.anionic.carboxylic.acid-coated.particles.
163
QD.concentration.is.another.parameter.that.requires.more.consideration..In.a.study.by.
Hoshino.et.al.
164
.EL-4.cells.were.incubated.with.different.concentrations.of.CdSe-ZnS-SSA.
