Biomedical Engineering Reference
In-Depth Information
a.gold.nanoparticle.by.measuring.the.mean.diameter.(d).of.the.AuNP.core.and.volume.of.
Au.atoms.(V
Au
),.following.Leff's.model:
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.
N
Au
.=.4.π.(d/2)
3
/V
Au
3.5 BiomedicalApplications
3.5.1 Therapeutics
3.5.1.1 Drug Delivery
Owing.to.their.high.surface-to-volume.ratio,.optical.tunability,.low.cytotoxicity,.and.ability.
to.interact.with.organic.molecules,.AuNPs.can.serve.as.excellent.vehicles.for.drug.delivery..
The.high.surface-to-volume.ratio.allows.for.a.large.amount.of.drugs.to.be.loaded.onto.the.
same.nanoparticle,.and.the.surface.properties.of.the.gold.nanoparticles.can.be.tuned.to.
alter. hydrophobicity.and.charge,. improving.cellular. uptake..In.addition,.AuNPs.readily.
form.strong.linkages.with.thiols,.which.can.be.used.to.link.gold.nanoparticles.with.other.
molecules..By.using.AuNPs.as.drug.delivery.carriers,.a.higher.concentration.of.the.drug.
can. be. delivered. to. the. speciic. cells. or. tissues. with. higher. eficiency. and. less. systemic.
adverse.effects.
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3.5.1.1.1 Surface Modiication
In.order.for.an.AuNP.to.be.able.to.carry.a.drug,.surface.modiication.is.irst.performed.to.
enable.its.conjugation.to.the.selected.molecule,.as.well.as.to.increase.its.biocompatibility.and.
stability..AuNPs.are.modiied.according.to.the.application.in.which.they.will.be.utilized.
and.to.the.desired.molecule.to.be.attached.to.the.nanoparticles..Surface.modiication.is.done.
to.increase.water.solubility.of.the.AuNPs,.prevent.their.aggregation,.as.well.as.prevent.or.
slow.down.their.uptake.by.the.reticuloendothelial.system.(RES),.thereby.increasing.their.
circulation.lifetime.
63,64
.It.allows.for.further.functionalization.of.the.AuNPs.with.conjugates.
such.as.antibodies,.biosensors,.and.other.ligands,.and.may.also.be.done.to.remove.or.replace.
original.capping.agents.
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.For.example,.the.seed-mediated.growth.method.produces.gold.
nanorods.capped.with.CTAB,.which.is.cytotoxic,
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.but.can.be.replaced.via.thiol.exchange.
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Surface.modiication.occurs.by.covalent.bond.formation.or.by.noncovalent.interactions..
Though.the.covalent.bonds.are.stronger,.they.are.also.plagued.with.loss.of.structural.integ-
rity. of. the. conjugate. and. dificulty. in. drug. release,. and. while. noncovalent. interactions.
offer.more.lexibility,.they.may.also.be.less.stable..Surface.modiication.strategies.include.
directly.linking.the.biomolecules.to.the.AuNPs,.or.functionalizing.the.biomolecules.with.
thiol.linkers.irst,.and.then.allowing.them.to.react.with.the.AuNPs..Other.strategies.depend.
on.hydrophobic.interactions.and.electrostatic.adsorption,.in.a.layer-by-layer.manner,.to.coat.
the.surface.of.the.AuNPs..For.example,.AuNPs.can.be.coated.with.poly(sodium-4-stryrene-
sulfonate).(PSS)..PSS.is.anionic.and.changes.the.surface.charge.of.the.AuNPs.from.positive.
to.negative,.allowing.their.further.conjugation.to.antibodies,.or.other.proteins.and.biomole-
cules.with.positively.charged.groups
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.(Figure 3.2D)..On.the.other.hand,.direct.electrostatic.
adsorption.can.occur.at.pH.values.higher.than.the.protein's.isoelectric.point,.causing.it.to.
become.negatively.charged.and.enabling.its.attachment.to.the.AuNPs.
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In. other. cases,. the. surface. modiication. occurs. during. the. synthesis. of. the. AuNPs,. as.
opposed. to. postsynthesis.. For. example,. the. Brust-Schiffrin. method. produces. thiolated.
