Biomedical Engineering Reference
In-Depth Information
24.2.2.1.1 Passive Targeting
This.approach.occurs.via.the.extravasation.of.the.nanoparticles.at.the.disease.site,.where.
the. fast-growing. tumor. microvasculature. is. leaky. with. defective. architecture,. which. is.
highly. permeable. to. macromolecules. relative. to. normal. tissue.
17
. The. dysfunctional. lym-
phatic.drainage.system.of.the.disease.cell.allows.for.the.enhanced.permeation.and.reten-
tion.(EPR).effect,
18
.as.a.result.of.which.nanoparticles.accumulate.at.the.tumor.site..For.this.
mechanism.to.take.place,.the.size.and.surface.of.the.nanoparticles.should.be.engineered.
such.that.they.circumvent.uptake.by.the.reticuloendothelial.system.(RES).
19
.One.way.of.
achieving.passive.targeting.is.the.use.of.direct.local.delivery.of.the.agents.into.the.affected.
cell..This.method.is.advantageous.since.it.preserves.the.drug.from.systemic.circulation,.
but.is.also.very.invasive.since.it.involves.injections.and.surgical.procedures..The.size.of.
open.interendothelial.gap.junctions.and.transendothelial.channels.determines.the.extent.
of.the.nanoparticle.extravasation,.with.a.cutoff.of.between.400.and.600.nm.reported.else-
where.
20
.One.of.the.biggest.challenges.for.passive.targeting.is.the.inability.to.accumulate.
large.enough.amounts.of.the.nanoparticles.on.the.tumor.cells,.resulting.in.low.therapeutic.
eficacy. and. drawing. unwanted. systemic. adverse. effects.
21
. Extended. circulation. time. is.
also.required.for.passive.targeting.to.allow.the.drug-loaded.nanoparticles.to.pass.the.dis-
ease.site.repeatedly.to.deposit.effectively.
24.2.2.1.2 Active Targeting
Localized.diseases.such.as.cancer.and.inlammation.overexpress.some.epitopes.or.recep-
tors.that.can.be.used.as.speciic.targets.
17
.The.use.of.nanoparticles.involves.the.conjugation.
of.the.targeting.molecules.on.the.surface.that.recognizes.and.attaches.to.speciic.receptors.
that.are.unique.to.a.particular.disease.cell..This.targeting.approach.is.based.on.interac-
tions.such.as.lectin-carbohydrate,.ligand-receptor,.and.antibody-antigen..Active.targeting,.
which.is.ligand.dependent,.is.particularly.invaluable.to.therapeutics.that.are.not.taken.up.
easily.by.cells..It.has.also.been.demonstrated.that.active.targeting.improves.the.distribution.
of.nanomedicines.within.the.tumor.interstitium.
22
.A.factor.to.be.considered.when.select-
ing. the. targeting. ligand. is. its. immunogenicity.. If,. for. example,. antibodies. expose. their.
constant.regions.on.the.liposomal.surface,.they.become.more.susceptible.to.Fc-receptor-
mediated. phagocytosis. by. the. mononuclear. phagocytic. system. (MPS).
23
. This. method. is.
particularly.useful.for.primary.tumors.that.have.not.yet.metastasized..One.of.the.major.
issues. in. chemotherapy. is. multiple. drug. resistance. (MDR),. which. often. starts. from. the.
overexpression.of.the.plasma.membrane.P-glycoprotein.(Pgp).in.cancer.cells.
24
.Pgp.acts.as.
an.eflux.pump.to.extrude.positively.charged.xenobiotics,.which.include.many.anticancer.
drugs,. out. of. the. cells.. Glycoproteins. are. known. to. be. unable. to. remove. polymer-drug.
conjugates.that.enter.the.cell.via.endocytosis,.and.this.renders.the.active.targeting.mecha-
nism.an.alternative.route.to.overcoming.MDR.
25
24.3 TheImportanceofNobleMetalNanoparticles
or Monolayer-ProtectedClusters(MPCs)
24.3.1 Essential Properties
It.appears.that.gold.and.silver.nanoparticles.could.probably.be.the.most.widely.studied.
materials.in.nanotechnology.to.date,.due.to.their.stability,.ease.of.preparation,.and.unique.
optical.properties.
26-33
.In.fact,.the.unusual.optical.properties.of.gold.and.silver.nanoparticles.
