Biomedical Engineering Reference
In-Depth Information
lymph.nodes. 139 .For.studying.the.anatomy.and.low.within.the.lymphatic.system,.ive.dif-
ferent.QDs.with.distinct.visible-range.emissions.have.been.used.for.in.vivo.real-time.mul-
ticolor.lymphatic.imaging.in.the.neck.and.axiliary.region.of.mice..This.method.enabled.
simultaneous. and. separate. monitoring. of. multiple. lymphatic. basins. in. real. time,. which.
was.possible.for.up.to.at.least.7.days. 140
QDs.have.also.been.used.as.potent.luorescent.angiography.contrast.agents.to.passively.
image.the.vascular.systems.of.different.animal.models..Through.the.use.of.multiphoton.
microscopy,.capillaries.as.deep.as.several.hundred.micrometers.have.been.imaged.through.
the.intact.skin.of.a.living.mouse.injected.with.green.light-emitting.QDs. 31 .The.coronary.
vasculature.has.also.been.visualized.by.Lim.et.al..by.intravenous.injection.of.NIR-(CdTe)
CdSe.QDs.into.an.adult.rat. 38 .In.another.study,.red.QDs.were.used.for.monitoring.vascu-
lature.development.in.transparent.zebra.ish.embryos..As.a.result,.QDs.enabled.obtaining.
comparable. details. of. the. embryonic. pattern. of. vasculogenesis,. ranging. from. early. dif-
ferentiation.to.the.late.larval.stages,.as.the.QDs.marked.the.newly.formed.vessels. 110
In. order. to. generate. contrast. at. speciied. locations,. QDs. should. be. effectively,. specii-
cally,.and.reliably.directed.to.intended.sites.without.any.alteration..In.a.pioneering.study,.
demonstrating.that.QDs.can.be.targeted.in.vivo.with.a.high.level.of.speciicity,.Akerman.
and.co-workers 79 .conjugated.CdSe-ZnS.nanoparticles.with.tissue-speciic.peptides..These.
conjugated.QDs.were.then.injected.to.breast.carcinoma.xenograft-bearing.nude.mice.for.
targeting.lung.vasculature,.tumor.blood.vessels,.or.tumor.lymphatic.vessels..Ex.vivo.his-
tological. analysis. revealed. that. QDs. speciically. homed. into. the. tumor. vasculature. and.
targed. organs,. but. not. to. the. surrounding. tissues,. guided. by. the. surface. peptide. mol-
ecules..NIRQD-RGD 141 .have.also.been.utilized.for.imaging.of.tumor.vessels.by.targeting.
integrin.a v b 3 ,.a.cell.adhesion.molecule,.which.is.overexpressed.on.the.surface.of.invasive.
cancerous.cells.and.most.tumor.vasculature,.but.not.in.quiescent.endothelium.and.nor-
mal.tissues. 142,143 .NIR.vasculature.imaging.has.been.successfully.achieved.by.intravenous.
administration.of.QD705-RGD. in.athymic. nude.mice. having. subcutaneous. human.glio-
blastoma. tumors.. Integrin-targeted. NIR. luorescence. imaging. has. introduced. new. per-
spectives.in.cancer.diagnosis,.as.well.as.image-guided.surgery.and.therapy. 141
Despite.all.advantages.of.using.NIR-QDs.for.deep.tissue.imaging,.whole.animal.opti-
cal. imaging. is. still. limited. due. to. low. excitation. eficiency. and. signiicant. background.
autoluorescence.. Short. wavelengths. that. are. required. for. the. eficient. excitation. of. any.
QDs. suffer. from. the. inability. of. deep. tissue. penetration,. so. that. the. amount. of. incident.
excitation.light.that.reaches.the.luorescent.probe.is.reduced.along.with.the.endogenous.
luorophore. excitation.. Bioluminescence. resonance. energy. transfer. (BRET),. which. con-
verts.chemical.energy.into.photon.emission,.has.been.used.to.circumvent.the.issues.asso-
ciated.with.an.external.excitation.source,.by.creating.self-illuminating.QDs..In.the.study.
performed.by.Rao.and.co-workers,.multiple.molecules.of.Luc8,.a.variant.of. Rotylenchulus
reniformis .luciferase,.were.covalently.conjugated.to.a.single.QD..Oxidation.of.coelentera-
zine,.the.substrate.of.luciferase,.via.its.binding.results.in.blue.light.emission,.which.could.
subsequently.excite.the.conjugated.nanoparticle.due.to.the.complete.overlap.between.Luc8.
emission.and.QD.absorption.spectra..In.vivo.imaging.of.administered.bioluminescent.QD.
conjugates.emitting.long.wavelengths.demonstrated.the.feasibility.of.multiplex.molecular.
imaging. in. small. animals. with. the. highly. enhanced. signal-to-background. ratio,.and. no.
background.in.nonsupericial.locations. 59,144,145 .One.of.the.important.issues.that.should.be.
addressed.before.the.widespread.utilization.of.bioluminescent.QD.technology.for.in.vivo.
imaging.is.targeting.speciicity,.considering.the.fact.that.a.majority.of.QD.surface.areas.
are.covered.by.luciferase.molecules,.and.so.there.should.be.plenty.of.space.for.targeting.
biomolecules. 24
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