Biomedical Engineering Reference
In-Depth Information
24.6 ToxicityIssues
Deinite.metabolic.and.immunogenic.responses.to.induction.abilities.by.nanomaterials.are.
currently.poorly.understood..This.is.in.contrast.to.common.chemical.compounds.(drugs.
and. therapeutics). that. are. routinely. subjected. to. well-established. toxicological. testing.
prior.to.public.release,.a.scenario.missing.for.nanomaterials.
134
.In.light.of.these.shortfalls.
and.the.sporadic.conlicting.reports.of.similar.nanomaterials.reported.as.both.toxic
135
.and.
nontoxic,
136
. concerted. efforts. have. therefore. been. dedicated. to. the. elucidation. of. nano-
materials.toxicity..The.toxicity.of.nanomaterials.has.been.approached.in.a.three-pronged.
strategy:
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.
1.. Composition. of. the. nanoparticles:. The. nanomaterials. can. be. composed. of. toxic.
materials.such.as.CdSe,.which.upon.corrosion.inside.an.organism.can.release.toxic.
ions.that.will.eventually.poison.the.cell.
138
.Compared.to.the.corresponding.bulk.
materials,.partial.decomposition.and.release.of.ions.is.highly.likely.for.nanosized.
CdSe.due.to.the.large.surface-to-volume.ratio.
.
2.. Chemical. properties. of. the. nanoparticles:. Nanoparticles. have. been. shown. to.
adhere. to. cell. membranes
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. and. also. be. ingested. by. cells.
140
. The. breaching. of.
the. cell. membrane. and. intracellular. storage. may. have. a. negative. effect. on. cells,.
regardless.of.the.toxicity.of.the.particles.and.their.subsequent.functionality.
.
3.. Nanoparticle.morphology:.Distinctly.shaped.materials.such.as.carbon.nanotubes.
can.rip.cells.like.needles.
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.This.in.turn.suggests.that.nanomaterials.of.the.same.
composition.would.have.different.biologic.responses.for.different.morphologies.
The.use.of.conventional.in.vivo.techniques.in.the.study.of.biologic.effects.and.cytotox-
icity.caused.by.nanomaterials.is.highly.informative.but.also.inherently.costly.and.labor-
intensive.
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. This. has. rendered
in. vivo
techniques. ill-suited. for. systematic. and. routine.
biologic. investigations. in. light. of. the. sheer. number. of. diverse. nanomaterials. currently.
in. development.. Various. mammalian. cell. culture. models. have. long. been. considered. as.
a. simpler,. more. cost-effective,. and. convenient. alternative. in. the. assessment. of. nanoma-
terials. toxicity,.compared.to.the.use.of.live.animal. models.
143
.Advantages. of.the.in.vitro.
approach.include.simplicity,.consistency.of.the.experimental.setup,.and.reproducibility.of.
the.experimental.results.
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.The.in.vitro.approach.encompasses.the.testing.of.viability.or.
luctuations.in.a.designated.inherent.biological.pathway.selected.against.the.nanomateri-
als.of.interest..Such.testing.is.also.motivated.by.the.ever-increasing.scope.of.applications.of.
engineered.nanomaterials.requiring.the.design.and.development.of.effective.and.reliable.
in.vitro.assays.
145,146
.Common.assays.for.toxicity.studies.use.measurements.of.triozonium.
salt. cellular. metabolic. activities. such. as. 3-(4,4-dimethylthiozol-2-yl)-2,5. diphenyl. tetra-
zonium. bromide. test. (MTT),. cellular. plasma. membranes. such. as. lactate-dehydrogenase.
(LDH). release. assay,. or. the. activities. of. other. housekeeping. enzymes.
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. In. vitro. assays.
are.robust.in.nature.and.have.been.used.extensively.in.the.elucidation.of.mechanisms.of.
toxicity,. as. well. as. for. demonstrating. the. relevant. biological. processes. that. are. involved.
in.the.response.to.speciic.test.materials..In.vitro
measurements.of.apoptosis.as.a.form.of.
toxicity.elucidation.have.been.reported.in.the.literature.
148
.The.approach.was.based.on.the.
measurements.of.DNA.fragmentation.occurring.in.apoptotic.cells..Alternatively,.the.dis-
tinct.morphological.changes.accompanying.the.process.of.apoptosis.can.be.used.to.mea-
sure.apoptosis.as.a.function.of.the.light.scattering.properties.of.the.cells.(low.cytometry)..
