Biomedical Engineering Reference
In-Depth Information
with.an.amphiphilic.polymer..Ligand.exchange.involves.the.substitution.of.the.coordinat-
ing.hydrophobic.surfactants.on.the.nanocrystal.surface.with.heterobifunctional.ligands,.
each.presenting.a.surface.anchoring.moiety.to.interact.with.the.inorganic.QD.surface.(e.g.,.
thiol).and.an.opposing.hydrophilic.end.group.(e.g.,.hydroxyl,.carboxyl).to.achieve.water.
compatibility. 23,70-73 . Although. the. generated. QDs. are. useful. for. biological. assays,. ligand.
exchange.results.in.reduced.luorescent.eficiency.and.a.tendency.to.aggregate.and.pre-
cipitate.in.biological.buffers..In.order.to.alleviate.these.problems,.the.hydrophobic.QDs.are.
coated.with.amphiphilic.polymers. 45,74,75 .Due.to.the.protective.hydrophobic.bilayer.encap-
sulating.each.QD,.the.resulting.nanoparticles.are.water.soluble.and.highly.stable.for.long.
periods.of.time..Typically,.the.QDs.coated.with.amphiphiles.have.a.larger.hydrodynamic.
size.than.those.with.a.monolayer.of.ligand, 25 .which.could.be.a.drawback.when.construct-
ing.Förster.resonance.energy.transfer.(FRET).pairs,.or.for.in.vivo.applications.in.humans. 76
QD.synthesis.is.generally.followed.by.a.subsequent.step.to.functionalize.the.nanopar-
ticles..For.this.purpose,.certain.biomolecules,.such.as.oligonucleotides, 74,77,78 .proteins, 23,45,50 .
peptides, 79,80 . or. small. molecules, 22,41,81 . are. bound. to. the. surface. of. nanomaterials. either.
covalently. or. noncovalently.. The. relatively. large. surface. area. of. QDs. allows. simultane-
ous. attachment. of. various. functional. molecules,. including. targeted. moieties,. therapeu-
tic.agents,.and.imaging.probes,.providing.new.potential.for.many.clinical.therapies.and.
diagnostics.. In. most. cases,. the. biological. function. of. the. conjugated. molecules,. such. as.
the.ability.of.molecular.recognition,.is.preserved.upon.conjugation.to.colloidal.QDs..The.
oligonucleotides.conjugated.to.QDs.could.successfully.hybridize.to.their.complementary.
sequences. 74,77,78 .Several.peptides, 79,80 .proteins, 23,82 .and.antibodies 45,50,80 .have.also.been.spe-
ciically.targeted.by.certain.bioconjugated.QDs. 83
There. are. several. determining. factors. that. should. be. controlled. during. nanomaterial.
bioconjugation,.including.the.ratio.of.biomolecules.per.QD.surface,.their.orientation,.the.
interval. distance. between. biomolecule. and. QD. surface,. and. the. strength. of. the. biomol-
ecules'.attachment. 44 .So.far,.none.of.the.current.methods,.such.as.bifunctional.linkage, 23 .
silanization, 22 . incorporation. in. micro-. or. nanobeads, 84 . and. hydrophobic. or. electrostatic.
interactions, 48,70 . have. fulilled. all. of. these. criteria. together,. so. that. any. single. or. speciic.
conjugation.strategy.has.its.own.particular.advantages.and.disadvantages.
2.6 ExtracellularandIntracellularTargeting
Typically,. QD. surface. functionalization. is. carried. out. to. achieve. extracellular. or. intrac-
ellular. targeting;. however,. there. are. some. intracellular. delivering. methods,. such. as.
microinjection,. electroporation,. and. nonspeciic. endocytosis,. that. do. not. require. any.
bioconjugation. 28,50,85
QDs.conjugated.with.particular.targeting.molecules,.such.as.proteins,.antibodies,.and.
ligands,.are.utilized.for.labeling.different.biomarkers.that.are.only.expressed.on.the.surface.
of.interested.cells. 30,86,87 .One.classical.example.in.which.speciic.antigens.on.cellular.mem-
brane.were.effectively.targeted.with.conjugated.QDs.is.the.localization.of.a.QD-secondary.
antibody.conjugated.to.Her2,.an.overexpressed.growth.factor.receptor.on.the.surface.of.
human.breast.cancerous.cells,.by.Bruchez.and.co-workers. 45,76 .In.another.study,.serotonin-
conjugated.QDs.were.targeted.to.neurotransmitter.receptors.expressed.on.human.epithe-
lial. kidney. cells. (HEK). cell. membrane. 81 . Lymphocytes. surface. antigens,. including. CD5,.
CD19,.and.CD45,.have.also.been.labeled.by.antibody-conjugated.QDs. 88
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