Biomedical Engineering Reference
In-Depth Information
intraoperative.imaging.
109,127
.Through.use.of.multiphoton.intervital.microscopy,.bone.mar-
row.precursor.cells.labeled.with.QD590-Tat.conjugates.(orange).have.been.tracked.as.they.
navigated.to.the.tumor.vessels.highlighted.with.QD470.micelles.(blue).
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.Multicolor.track-
ing.of.living.stem.cells.using.different-sized.QDs.could.be.limited.due.to.the.nanoparticle.
escape.in.which.small-sized.QDs.have.been.shown.to.rapidly.disappear.from.the.cells.
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.
Asymmetric.division,
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.which.results.in.nonequivalent.distribution.of.endosomes.between.
daughter.cells.and.leads.to.the.appearance.of.nonluorescent.cells,
98
.and.the.possibility.of.
uptake.of.the.tracing.agents.by.unlabeled.cells.after.cellular.death.or.leakage.through.gap.
junction.channels,.resulting.in.false.positive.data,
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.are.among.the.important.impediment.
factors. in. eficient. stem. cell. tracking. with. luorescent. nanoparticles.. In. order. to. evaluate.
possible.particle.transfer.from.loaded.to.unloaded.cells,.QD-hMSCs.were.cocultured.with.
hMSCs.transfected.to.express.GFP..The.results.indicated.no.evidence.of.QD.internalization.
by. GFP-expressing. cells,. which. was. consistent. with. the. known. diameters. of. QDs. (~10b.
nm). and. gap. junction. channels. (~1. nm).. Moreover,. incubation. of. canine. myocytes. with.
the.mechanically.disrupted.QD-hMSC.lysate,.in.order.to.simulate.the.in.vivo.condition.of.
dying.cells,.demonstrated.that.QD.clusters.were.not.internalized.by.cells.for.up.to.24.h.
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2.10 UsingQuantumDotsasOpticalContrastAgents
QDs.can.also.be.utilized.as.promising.contrast.agents.for.discerning.the.anatomical.struc-
tures. of. interest. from. surrounding. tissues,. and. thus. improving. the. signal-to-noise. ratio,.
which.is.highly.desired.in.diagnostic.imaging..Typically,.there.are.three.different.ways.for.
delivering.QD-based.contrast.agents.to.the.target.organ,.including.local.injection.and.non-
targeted. and. targeted. systemic. administration.
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. QDs,. similar. to. other. nanoparticles,. are.
nonspeciically.taken.up.by.the.reticuloendothelial.system.(RES),.which.is.mainly.located.
in. the. spleen,. liver,. and. lymph. nodes.. Consequently,. nontargeted. systemically. adminis-
tered.nanoparticles.will.eventually.be.accumulated.in.these.organs..For.most.of.the.uses.in.
vivo,.reducing.nonspeciic.QD.uptake.and.prolonging.their.circulation.lifetime.is.essential..
Exceptions. are. settings. that. require. deining. some. tumor. types. or. detection. of. sentinel.
lymph. nodes.. In. these. situations,. rapid. deposition. in. RES. is. potentially. useful.
32
. It. was.
demonstrated.by.Ballou.et.al..that.the.half-life.of.QDs.in.the.bloodstream.of.mice.is.mark-
edly.increased.by.the.use.of.long-chain.polyethylene.glycol.(PEG).surfaces,
32
.an.effect.that.
also. has. been. documented. for. other. types. of. nanoparticles. and. small. molecules.. This. is.
attributed,.in.part,.to.the.reduced.nonspeciic.adsorption.and.decreased.antigenicity.of.the.
nanoparticles.
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.The.hydrodynamic.diameter.has.also.been.considered.an.effective.param-
eter. for. particle. distribution. kinetics. and. their. clearance. from. the. organism,
27
. in. which.
larger.particles.are.cleared.much.faster.from.the.circulation.than.smaller.particles,.which.
are.more.likely.to.be.taken.up.by.other.cells.within.the.body,.including.targeted.cells.
131
2.11 TumorTargetingandImaging
One.of.the.important.potential.uses.of.QDs.is.for.the.speciic.and.effective.detection.of.par-
ticular.cells.via.recognition.of.their.unique.markers..These.properties.have.opened.new.
possibilities. for. tumor. targeting. and. imaging,. as. some. speciic. markers. are. particularly.
