Biomedical Engineering Reference
In-Depth Information
delivery.challenges..Nanoparticulate.materials,.including.biodegradable.polymeric.nano-
particles,. dendrimers,. nanoshells,. spheres,. and. others,. can. all. be. actively. conjugated. to.
speciic.biomolecules.for.delivery..Grafting.of.amphiphilic.polymers.such.as.PEG.improves.
the.systemic.circulation.times.and.bioresistance.properties..Factors.such.as.the.biological.
environment,.target.cell.surface.receptors,.molecular.mechanisms,.and.pathobiology.of.the.
disease.should.all.be.considered.in.the.delivery.hybrid.materials..These.factors.translate.to.
material.dose.and.retention.time,.stability.in.the.target.environment.(cell,.tissue,.or.organ),.
disease.progression.(alterations.in.the.drug.target.composition),.and.biocompatibility.and.
eficient.release.kinetics..A.cross-sectional.preamble.into.the.different.targeting.molecules.
(in.addition.to.antibodies.discussed.above).is.briely.discussed..Aptamers,.which.rival.the.
commonly. abundant. use. of. antibodies. in. diagnostics. and. therapeutics,. have. also. been.
explored.in.the.diagnostic/detection.strategies.for.cancer. 118 .These.molecules.are.DNA.or.
RNA.oligonucleotides.that.fold.by.intramolecular.interactions.into.unique.conformations.
with.ligand-binding.characteristics. 119 .An.A10.aptamer.has.been.reported.conjugated.with.
nanoparticles.for.the.speciic.targeting.of.prostate-speciic.membrane.antigen.(PSMA), 120 .a.
transmembrane.protein.upregulated.in.many.cancer.types..In.vivo.evaluation.for.LNCap.
prostate. cancer,. expressing. PMSA. antigens,. showed. tumor. size. regression. in. a. 109-day.
intratumor.single-injection.experiment..Other.aptamer-nanoparticle.conjugates.have.been.
reported.for.colometric.assays.for.the.detection.of.platelet-derived.growth.factor.(PDGF).
and.its.receptor.using.Au-NP-aptamer.conjugates. 121 .A.strategy.based.on.oligopeptides.has.
been.identiied.as.a.powerful.route.for.targeting.strategies..As.an.alternative.to.antibod-
ies,. the. small-sized,. low-immunogenic,. and. highly. stable. short. peptides. have. garnered.
exceptional. attention,. with. combinatorial. libraries. leading. to. the. identiication. of. short.
peptides.with.varied.capabilities.for.binding.targeted.proteins,.cells,.or.tissue.with.high.
speciicity. 122 .A.cyclic.peptide.arginine-glycine-aspartic.acid.(RGD).that.binds.speciic.inte-
grins.on.cancer.cell.surfaces.is.currently.in.phase.II.trials.for.the.treatment.of.non-small-
cell.lung.cancer.and.pancreatic.cancer. 123 .Another.strategy,.based.on.the.overexpression.of.
speciic.epitopes.on.cancerous.cells,.is.the.small.vitamin.folic.acid.(folate),.which.binds.to.
surface.folate.receptors.(FRs).with.high.afinity.(KD.=.∼10 -9 .M)..This.allows.for.derivatiza-
tion.of.different.delivery.nanoparticulate.materials.with.folic.acid.for.delivery.into.cancer-
ous. cells. without. harming. healthy. populations,. via. FR-mediated. endocytosis. 124 . Due. to.
the.expression.of.the.folate.receptors.in.other,.healthy.epithelial.cell.types,.such.as.in.the.
choroids.plexus,.placenta,.lung,.intestine,.and.kidney,.FR-mediated.nanoparticle.delivery.
techniques.are.still.subject.to.reinement.for.increased.selectivity..Hybrid.combinations.of.
these. different. targeting. platforms. with. noble. metal. particles. of. nominal. sizes. present. a.
viable.and.versatile.toolbox.for.the.targeted.delivery.of.cargoes.into.cancerous.cells,.tis-
sues,.or.organs.
24.4.2 Photothermal Cancer Therapy
The.mainstream.approaches.in.the.treatment.of.cancer,.such.as.surgery,.chemotherapy,.and.
radiotherapy,. present. some. persistent. drawbacks. in. their. line. of. operation.. Surgery. can.
only.be.effective.for.a.physically.accessible.tumor,.chemotherapy.has.numerous.side.effects,.
and.radiotherapy.is.highly.invasive.to.healthy.cells.in.the.line.of.radiation..Therefore,.there.
is.a.need.for.the.development.of.alternative.methods.in.the.optical.heating.arena.by.depos-
iting.photoabsorbers.within.cancer.cells.and.applying.optical.heating.for.tumor.ablation. 125 .
Gold.nanoparticles.are.known.as.fast-rate.converters.of.light.energy.into.heat. 126 .With.the.
gold. nanoparticles. possessing. much. higher. absorption. cross. sections. than. conventional.
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