Biomedical Engineering Reference
In-Depth Information
in.more.depth.later.in.this.chapter.and.are.based.on.a.representative.therapeutic.that.is.a.
perluorocarbon.nanoemulsion.
4.2.4 Perfluorocarbon Nanoparticle Emulsion
Perluorocarbons.(PFCs)—hydrocarbons.with.all.the.hydrogen.atoms.replaced.with.luo-
rine.atoms—exhibit.a.unique.combination.of.properties,.including.exceptional.inertness,.
stability,. low. surface. tension,. simultaneous. hydrophobicity. and. lipophobicity,. and. high.
gas-dissolving.capacity.
26
.They.are.therefore.of.particular.interest.to.biomedical.research,.
including. drug. delivery,. oxygen. therapy,. and. artiicial. blood. substitutes.
27,28
. One. of. the.
very.irst.successful.targeted.imaging.nanoparticles.was.a.liquid.PFC.emulsion.based.on.
an.artiicial.blood.substitute.
29
.It.followed.the.generic.nanoparticle.paradigm,.having.a.liq-
uid.core.(approximately.250.nm).encapsulated.with.a.lipid.monolayer.into.which.various.
components.for.imaging.and.targeting.could.be.inserted..Originally,.it.was.a.site-targeted.
ultrasound.agent,.relying.on.the.differing.speeds.of.sound.between.water.and.the.PFC.to.
generate.relections.from.the.layer.of.nanoparticles.bound.to.the.target..Later,
30
.the.outer.
membranes. of. the. nanoparticles. were. decorated. with. gadolinium. diethylene-triamine-
pentaacetic.acid.(Gd-DTPA),.a.common.contrast.agent.for.MRI..Unlike.previous.targeted.
MRI.contrast.agents,.this.vehicle.delivered.over.90,000.copies.of.the.gadolinium.chelate.to.
each.binding.site,.thereby.overcoming.the.poor.sensitivity.of.MRI.to.low.concentrations.
of.Gd-DTPA..This.basic.nanoparticle.platform.has.been.the.backbone.from.which.many.
similar.constructs.have.been.developed.for.applications.in.ultrasound,
29
.CT,
31
.MRI,
32
.and.
even. multiple. imaging. modalities. with. one. agent.
33
. By. incorporating. multiple. markers.
or.different.perluorocarbons,.this.system.allows.multicolor.detection.of.multiple.targets.
simultaneously.
34
4.3 DetectingMarkersofDisease
The.goal.of.a.diagnostic.nanoparticle.contrast.agent.is.to.home.to.markers.of.disease.and.
be.detected,.preferably.in.a.quantitative.way,.by.the.clinically.relevant.imaging.technique..
The.biomarker.needs.to.identify.speciically.a.disease.early.in.its.course..The.irst.incarna-
tions. of. the. PFC. nanoparticle. contrast. agent. were. targeted. to. ibrin.. Detecting. exposed.
ibrin.associated.with.atherosclerotic.plaque.can.help.distinguish.the.difference.between.
lesions.that.are.restricting.the.lumen.but.are.stable.and.those.at.increased.risk.for.disas-
trous.rupture.
35,36
.In.atherosclerosis,.many.other.markers.point.to.the.disease,.some.at.a.
much.earlier.stage.than.plaque.rupture..One.such.early.indicator.(which.is.not.only.spe-
ciic,.but.a.requirement.for.disease.progression).is.angiogenesis.within.the.
vasa vasorum
.
37
.
Angiogenesis.is.a.complex.process.with.many.molecular.signatures..One.of.those,.which.
holds.a.critical.role.in.new.blood.vessel.formation,.the.α
ν
β
3
.integrin,.has.garnered.much.
attention.as.a.target.
38
Targeting. paramagnetic. PFC. nanoparticles. to. the. α
ν
β
3
. integrin,. Winter. et. al.. demon-
strated. the. ability. to. image. and. quantify. with. MRI. early-stage. atherosclerosis.
39
. In. these.
experiments,.the.heterogeneous.nature.of.the.disease.was.clearly.visible.along.the.length.
the.aorta..However,.in.control.subjects,.in.which.the.disease.was.not.present.or.else.non-
targeted. contrast. agent. was. administered,. no. signal. enhancement. was. appreciated.. The.
