Biomedical Engineering Reference
In-Depth Information
AuNPs.stabilized.by.4-mercaptophenol.(Figure 2.3B),.with.a.size.range.from.1.5.to.6.nm.
35
.
The.citrate.reduction.method.also.yields.citrate-capped.AuNPs.that.can.be.directly.conju-
gated.to.biomolecules.(Figure 2.3A)..AuNPs.can.bear.a.negative.or.positive.charge.during.
synthesis.by.reduction.of.HAuCl
4
.in.the.presence.of,.for.example,.citrate.or.2-aminoethane-
thiol,.respectively
34,67
;.or.postsynthesis.by.functionalization.with.ligands.having.acidic.or.
amine.groups,.respectively.
68
Niidome.et.al.
66
.studied.the.biodistribution.of.polyethylene.glycol.(PEG).versus.non-PEG.
AuNPs..After.0.5.h,.54%.of.the.PEG.NPs.were.found.in.the.blood,.and.after.72.h,.35%.were.
found.to.have.accumulated.in.the.liver;.with.the.non-PEG.NPs,.30%.accumulation.in.the.
liver.occurred.after.only.0.5.h..The.length.of.the.PEG.chains.affects.the.stabilizing.capacity.
of.PEG.for.AuNPs.in.circulation,. where.shorter.chains. of.molecular. weight. below. 2,000.
were.found.to.have.lower.capacity..Another.role.for.PEG.is.to.be.used.as.a.spacer.between.
the.AuNP.and.conjugated.molecules,.improving.access.to.their.targets.
69
.This,.for.example,.
causes.a.conjugated.oligonucleotide.to.be.spaced.farther.away.from.the.AuNP,.increasing.
the.accessibility.of.the.oligonucleotide.for.hybridization.with.its.target.(Figure 3.2C).
Thiolated. PEG. is. also. used. to. replace. the. CTAB. surfactant. on. gold. nanorods.
66
.
Pegylation.bestows.higher.bioavailability.and.lower.immunogenicity.and.uptake.by.RES.
on.AuNPs.
70,71
.Surface.modiication.using.alkanethiol-terminated.PEG.chains.at.low.con-
centrations.results.in.a.mushroom-shaped.conformation,.while.high.concentrations.result.
in.a.brush-like.conformation
72,73
.(Figure 3.3C.and.D).
3.5.1.1.2 Types of Targeting
There.are.two.ways.by.which.cancer.cells.can.be.targeted:.passive.and.active.targeting,.
the.latter.being.more.tumor.cell.speciic
74,75
.(Figure 3.4)..Drugs.may.be.delivered.via.active.
targeting,.passive.targeting,.or.a.combination.of.both,.and.once.the.AuNPs.have.reached.
their.target.destination,.drug.release.can.be.triggered.by.internal.or.external.stimuli.
In. passive. targeting,. the. leaky. vasculature. surrounding. malignant. cells
75-77
. and. dys-
functional.lymphatic.drainage
78,79
.allow.particles.of.sizes.up.to.400.nm.to.extravasate.and.
accumulate. in. the. tumor,
79,80
. an. effect. known. as. enhanced. permeability. and. retention.
(EPR)
77,78
.(Figure 3.4)..However,.not.all.tumors.show.EPR,
81
.and.passive.targeting.does.not.
enable.the.targeting.of.single.cells.or.small.tumors.
82
Active. targeting,. on. the. other. hand,. uses. molecular. recognition. by. conjugating. the.
AuNPs.to.molecular.probes,.such.as.antibodies.or.other.ligands.(Figure 3.2),.which.bind.
speciically.to.the.targeted.cells
83-85
.(Figure 3.4).
Folate.can.be.used.for.cancer.cell.targeting..Folate.is.a.precursor.needed.by.cells.for.nucleic.
acid.synthesis.and.is.overexpressed.by.ovarian,.breast,.lung,.brain,.kidney,.prostate,.colon,.
and.some.myeloid.cancer.cells,.among.others..Normal.cells.also.express.folate.receptors,.
but.on.the.apical.surface.of.their.polarized.epithelium..This.polarization.is.lost.with.malig-
nant.transformation,.and.the.folate.receptors.become.accessible.to.blood-borne.molecules.
through. the. vascular. epithelium.
86
. Therefore,. only. the. overexpressed. folate. receptors. of.
malignant.cells.are.targeted,.while.folate.receptors.of.normal.cells.are.protected.
86
Bhattacharya.et.al.
86
.modiied.5.nm.gold.nanospheres.with.polyethylene.glycol.(PEG)-
amines. and. PEG-thiols. and. further. functionalized. them. with. folic. acid. through. nonco-
valent.interactions.to.target.folate.receptors.on.ovarian.and.multiple.myeloma.cancer.cell.
lines..AuNPs.modiied.with.PEG-amines.had.a.better.binding.capacity.and.drug.release.
proile. than. those. modiied. with. PEG-thiols.. Cancer. cell. lines. that. overexpressed. folate.
receptors.the.most.showed.the.highest.uptake.of.the.folic.acid.conjugates.
