Biomedical Engineering Reference
In-Depth Information
Shukla. et. al.
167
. studied. macrophage. interactions. with. AuNPs. and. found. no. secretion. of.
pro-inlammatory. cytokines. when. the. AuNPs. were. internalized. by. the. macrophages..
Internalization.of.AuNPs.also.did.not.disrupt.cellular.function..The.authors.concluded.that.
AuNPs. are. biocompatible,. noncytotoxic,. and. nonimmunogenic,. and. have. an. antioxidant.
effect.by.reducing.reactive.oxygen.and.nitrite.production..Connor.et.al.
168
.studied.the.uptake.
and.toxicity.of.18.nm.AuNPs.in.human.leukemia.cells,.with.no.signiicant.observations.of.
acute.toxicity.caused.by.the.AuNPs.themselves,.though.toxicity.may.be.caused.by.AuNP.pre-
cursors..In.addition,.in.vivo.studies.by.Cho.et.al.
169
.revealed.that.13.nm.PEG.AuNPs.caused.
acute.but.transient.inlammation.in.the.liver.cells.of.mice,.marked.by.increased.neutrophil.
inlux,.and.apoptosis.7.days.after.a.single.injection.of.AuNPs.in.a.dose-dependent.manner..
AuNPs.accumulated.most.in.the.liver.and.spleen.due.to.trapping.by.Kupffer.cells.and.spleen.
macrophages,.respectively,.showing.a.tendency.for.accumulation.in.organs.with.phagocytic.
activity..Other.organs,.such.as.the.kidneys,.lungs,.and.brain,.showed.gradual.clearance.of.the.
AuNPs..The.authors.concluded,.however,.that.AuNPs.did.not.cause.acute.cytotoxicity.
Balasubramanian.et.al.
170
.attributed.similar.indings.of.AuNP.accumulation.to.the.discon-
tinuous.endothelium.of.the.liver.and.spleen,.allowing.the.passage.of.AuNPs.of.up.to.100.nm.
to.enter.from.circulation,.and.to.the.opsonization.of.the.AuNPs,.where.binding.with.circu-
lating.antibodies.leads.to.their.uptake.by.the.RES..Accumulation.of.AuNPs.in.membrane-
barrier-controlled. environments. is. mainly. size. dependent.. For. example,. the. blood-brain.
barrier.allows.only.AuNPs.of.less.than.20.nm.to.pass.through.
171
.The.renal.glomerular.base-
ment.membrane.(GBM).also.blocks.out.aggregated.AuNPs.due.to.their.large.size..However,.
an.additional.mechanism.of.the.GBM.may.be.dependent.on.time.and.charge..In.general,.the.
kidney.excretes.AuNPs.in.the.urine.after.4-5.h.of.intravenous.(I.V.).injection,
148,170
.but.with.
time,.the.AuNPs.begin.to.accumulate..The.authors.hypothesized.that.the.AuNPs.become.
coated.with.negatively.charged.proteins.that.are.repelled.by.the.negatively.charged.GBM.
170
.
Moreover,.redistribution.of.the.AuNPs.occurred.after.1.month.of.administration.
The.same.study.reported.differences.in.distribution.according.to.the.route.of.administra-
tion,.where.less.accumulation.of.AuNPs.in.the.liver.was.observed.via.the.inhalation.route.
vs.. I.V.. injection.
170
. Another. study. examined. the. distribution. of. various. sizes. of. AuNPs.
administered.orally..Widespread.distribution.occurred.with.the.small.4.nm.AuNPs,.while.
the.larger.58.nm.AuNPs.were.limited.to.the.gastrointestinal.tract.
172
There.are.concerns.about.transplacental.distribution.of.AuNPs,.which.may.affect.fetal.
development. either. directly. or. indirectly. by. causing. placental. insuficiency.. Myllynen.
et al.
173
.examined.the.effect.of.15.and.30.nm.sized.PEG.AuNPs.within.a.6.h.time.period..
The.AuNPs.were.not.found.in.fetal.blood,.and.therefore.did.not.cross.the.placental.bar-
rier,.but.accumulated.instead.in.the.trophoblastic.layer..The.fate.of.these.AuNPs.after.6.h,.
however,.needs.to.be.monitored.to.see.if.their.accumulation.could.lead.to.placental.or.fetal.
adverse.effects..Another.study.compared.1.4.and.18.nm.sized.AuNPs.and.reported.that.
AuNPs.do.cross.the.placenta.in.a.size-dependent.manner.
174
3.7 FutureProspectsandChallenges
The.many.qualities.of.AuNPs.hailed.throughout.this.chapter.make.them.an.attractive.and.
versatile. tool. for. biomedical. applications.. Healthcare. resources. are. moving. toward. the.
development. of. more. cost-effective,. rapid,. and. less. invasive. options. for. patients.. AuNPs.
have.proven.to.be.useful.tools.in.fulilling.these.sought-after.beneits,.in.addition.to.offering.
