Gold Nanoparticles in Biomedicine - Bionanotechnology: Global Prospects - page 65

FIGURE 3.6
Drug. delivery. using. gold. nanorods.. The. gold. nanorod. is. conjugated. to. the. drug.. Upon. NIR. irradiation,. the.
nanorod.gradually.melts.into.a.nanosphere,.and.the.drug.is.released.
presence.of.these.agents.and.oxygen.(supplied.by.blood.and.tissues).leads.to.the.release.
of.cytotoxic.singlet.oxygen. 95,96 .However,.full.penetration.of.light.into.deep.tissue.tumors.
is.still.a.challenge, 95 .and.the.absence.of.oxygen,.such.as.in.tissue.hypoxia.with.bacterial.
infection,. renders. PDT. ineffective. 97 . Moreover,. because. these. agents. are. only. relatively.
speciic,.widespread.burns.of.the.tissues.containing.the.photosensitizers.may.occur.upon.
exposure.of.the.body.to.light. 95 .Hone.et.al. 98 .used.the.PDT.principle.by.functionalizing.2-4.
nm.AuNPs.with.pthalocyanines.(Pc),.which.act.as.photosensitizers.and.release.cytotoxic.
singlet.oxygen.upon.IR.light.stimulation..The.quantum.yield.of.the.AuNP-bound.Pc.was.
50%.higher.than.that.of.free.Pc.
3.5.1.1.5 Anticancer Drugs
3.5.1.1.5.1 Tumor Necrosis Factor (TNF) Tumor. necrosis. factor. (TNF). has. both. an. antican-
cer.and.antiangiogenesis.(new.vessel.formation).effect..Paciotti.et.al. 64 .functionalized.33.nm.
AuNPs.with.TNF.by.direct.conjugation.between.the.citrate.capping.on.the.AuNPs.and.the.
TNF.at.an.optimum.pH.between.8.and.10..Each.AuNP.was.able.to.carry.400.molecules.of.TNF,.
which.acted.as.both.a.targeting.and.therapeutic.agent.
3.5.1.1.5.2 Paclitaxel Gibson.et.al. 99 .functionalized.AuNPs.with.paclitaxel,.a.chemothera-
peutic. drug.. Hexaethylene. glycol. (HEG). was. linked. at. the. C7. position. of. paclitaxel,. act-
ing.as.a.carboxyl.linker,.and.covalently.bound.to.AuNPs.modiied.by.4-mercaptophenol..
HEG.is.expected.to.increase.water.solubility.of.the.functionalized.AuNPs.and.reduce.their.
uptake.by.the.RES,.thereby.increasing.circulation.lifetime..Each.AuNP.was.able.to.carry.
over.70.paclitaxel.molecules.
3.5.1.1.5.3 Methotrexate (MTX) Methotrexate.(MTX).is.an.analogue.of.folic.acid.that.dis-
rupts.cell.metabolism.by.inhibiting.dihydrofolate.reductase.and.other.enzymes.involved.
in.purine.synthesis..MTX.is.used.as.an.anticancer.drug-targeting.malignant.cell.that.over-
expresses.folate.receptors..Drawbacks.of.systemic.or.free.MTX.therapy.include.the.devel-
opment. of. cellular. resistance. via. decreased. uptake,. as. well. as. increased. eflux. of. MTX..
Chen. et. al. 100 . functionalized. 13. nm. colloidal. AuNPs. with. MTX. by. direct. conjugation. to.
target.Lewis.lung.carcinoma.cells..Both.the.citrate-capped.AuNPs.and.the.MTX.molecules.
are.negatively.charged.at.neutral.pH..At.higher.concentrations,.MTX.replaces.the.citrate.
capping.(Figure 3.2A)..The.MTX-AuNPs.were.found.to.eficiently.transport.the.drug.into.
the. cancer. cells. and. exert. their. cytotoxic. activity. in. a. faster. and. more. effective. manner.
than.that.observed.with.free.MTX.