Biomedical Engineering Reference
In-Depth Information
clearance.mechanisms..For.example,.iron.oxide.nanoparticles.(10-100.nm).are.cleared.by.
the.reticuloendothelial.system.(RES),.and.therefore.normally.accumulate.in.organs.of.the.
RES,. namely,. the. liver,. spleen,. lymph. nodes,. and. bone. marrow.. Similarly,. macrophages,.
which. are. prevalent. in. areas. of. interest,. such. as. tumors,
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. lymph. nodes,. and. atheroscle-
rotic.plaques,
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.will.take.up.nanoparticles.and.concentrate.them.for.imaging..Coating.the.
surface.of.nanoparticles.with.polyethylene.glycol.(PEG).chains.of.various.lengths.can.also.
affect.the.pharmacodynamics.
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Active.targeting.is.frequently.achieved.via.attaching.to.the.outer.surface.of.the.particle.
antibodies,.antibody.fragments,.aptamers,.peptides,.peptidomimetics,.or.other.small.mol-
ecules.that.have.an.afinity.for.the.binding.site.of.interest.
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.The.avidity.of.the.particle—
that.is,.its.ability.to.“stick.and.stay”.at.the.intended.binding.site—can.be.controlled.by.the.
way.the.targeting.ligand.is.put.on.the.nanoparticle,.the.number.of.ligands.per.particle,.and.
whether.or.not.the.ligands.are.free.to.move.along.the.surface.of.the.particle..The.targeting.
effectiveness.of.a.nanoparticle.is.determined.by.the.likelihood.that.a.nanoparticle.gets.to.
the.intended.site,.that.the.targeting.ligand.is.presented.to.the.complementary.moiety.in.
an.orientation.compatible.with.binding,.and.whether.more.than.one.ligand.will.bind.the.
nanoparticle. to. the. target.. Because. of. this. multifaceted. nature,. the. binding. afinity. of. a.
nanoparticle.construct.can.far.exceed.that.of.the.individual.component.targeting.ligands..
Through.phage.display
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.and.many.other.novel.techniques,.more.and.more.unique.recep-
tor.targeting.ligands.that.can.be.utilized.as.the.targeting.component.of.multicompartmen-
tal.nanoparticles.are.being.discovered.
4.2.2 Imaging
Just.as.the.targeting.ligand.is.one.component.of.these.multicomponent.nanoparticles,.so.
is. the. imaging. agent.. As. previously. stated,. a. major. strength. of. nanoparticle-based,. site-
targeted.imaging.contrast.agents.over.the.small.molecule.approach.is.that.multiple.copies.
of.the.imaging.constituent.can.be.embedded.in.the.core.or.attached.to.the.surface..From.a.
very.simplistic.perspective,.one.might.imagine.this.being.akin.to.the.difference.between.
shipping.a.single.lantern.to.a.given.postal.address.and.delivering.an.entire.truckload.of.
lanterns.to.the.same.address..The.latter.would.indeed.be.much.easier.to.spot.in.the.dark!
Nanoparticle.imaging.agents.have.been.developed.for.every.medical.imaging.technique,.
including.optical,.ultrasound,.magnetic.resonance.imaging.(MRI),.x-ray.computed.tomog-
raphy.(CT),.positron.emission.tomography.(PET),.and.single-photon.emission.computed.
tomography. (SPECT).. Often,. the. new. agents. are. constructed. by. “plugging. in”. existing.
imaging.agent.components,.such.as.chelates.of.radioisotopes.(i.e.,.for.nuclear.medicine).or.
lanthanides.(i.e.,.for.MRI).
4.2.3 Therapeutic Delivery
In.addition.to.delivering.a.truckload.of.imaging.agent.to.a.particular.locale,.nanoparticles.
have.the.ability.to.deliver.drugs..An.important.beneit.of.nanotechnology.is.the.repackag-
ing.of.drugs.to.control.the.biodistribution.and.pharmacodynamics.of.drug.release..More.
than.just.time-released.capsules,.nanotech.approaches.permit.entirely.new.methods.of.for-
mulating.drugs.with.the.potential.for.greater.safety.and.eficacy.
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.But.also,.because.drugs.
can. be. sequestered. into. nanoparticles. and. released. only. upon. binding. at. the. intended.
site—a. concept. described. as. contact-facilitated. drug. delivery
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—systemic. effects. can. be.
reduced. while. a. greater. local. concentration. is. achieved.. Examples. of. this. are. discussed.
