Biomedical Engineering Reference
In-Depth Information
and. preclinical. evaluation. in. animal. models.. The. application. of. nanotechnology. in. this.
area.could.introduce.a.component.of.miniaturization,.and.thus.improve.the.ability.to.fab-
ricate.massive.microarrays.in.small.spaces.using.microludic.technology.
24.2 TheNano-BioInterface
The.size.comparability.of.the.nanoparticles.(1-100.nm).with.those.of.most.biomolecules.
and. subcellular. components. makes. it. logical. for. the. interfacing. of. nanotechnology. and.
molecular.biology..Nanoparticles.have.received.a.lot.of.attention.recently.in.the.develop-
ment.of.imaging,.targeting,.diagnostic,.and.drug.delivery.and.discovery.in.both.in.vivo
and.
in.vitro
systems.
3,4
.Numerous.formulations.of.these.entities.have.raced.into.the.forefront,.
including. dendrimers,. nanocages,. micelles,. molecular. conjugates,. liposomes,. quantum.
dots,.and.nanoshells.
5
.The.design.of.stealth,.multiplexed.drug.delivery.and.imaging.sys-
tems.has.started.to.beneit.immensely.from.the.unique.versatility.of.nanoparticles.in.terms.
of. functionalities. and. impressive. optical. properties.
6
. In. vitro. and. in. vivo. labeling. using.
quantum.dots.has.also.been.reported.
7
.Intracellular.delivery.of.cargoes.into.the.nucleus.of.
the.cells.can.be.manipulated.by.conforming.the.nanoparticle.systems.to.a.few.guidelines:.
(1). the. nanoparticles. must. enter. the. cell. via. receptor-mediated. endocytocytosis. (RME);.
(2).they.must.evade.the.endosomal-lysosomal.pathways;.(3).they.must.possess.a.nuclear.
localization.signal.(NLS).for.successful.internalization;.and.(4).they.must.be.small.enough.
to. cross. the. nuclear. membrane.
8
. Attention. has. also. been. given. to. the. toxicity. effects. of.
these. entities. inside. a. living. organism.. For. slightly. larger. particles. (≥200. nm),. clearance.
has. been. reported. through. opsonization,. with. the. large. size. assisting. in. recognition. of.
the. nanoparticles. by. macrophages.
5
. The. incorporation. of. surface. functionalities. such. as.
polyethylene.glycol.(PEG).polymer.renders.these.nanoparticles.highly.biocompatible.and.
lowers.their.cytotoxicity.
24.2.1 Targeted Drug Delivery Systems
Concerted.efforts.have.of.late.been.focused.on.developing.novel.drug.carriers.that.can.
selectively. be. used. to. target,. label,. and. destroy. clinical. conditions. in. a. reproducible.
manner.. For. instance,. cancer. targeting. would. be. such. that. delivery. of. therapeutics.
targets. the. tumors,. killing. only. the. infected. cells. and. sparing. the. normal. cells.. These.
strategies. can. therefore. be. employed. in. new. and. existing. drugs,. thereby. improving.
their. therapeutic. index.. Three. common. requirements. have. been. identiied. for. a. suc-
cessful. carrier-based. delivery. strategy:. (1). prolonged. blood. circulation,. (2). suficient.
tumor. accumulation,. and. (3). controlled. drug. release. and. uptake. by. the. tumor. cells..
The.release.proile.of.these.hybrid.delivery.systems.must.also.be.designed.such.that.it.
matches.the.pharmacodynamics.of.the.drug.
9
.Nanoparticulate.carriers,.such.as.those.of.
noble.metals,.have.been.demonstrated.as.a.viable.alternative.for.the.delivery.of.targeted.
therapeutics.. The. surface. modiications. of. nanocarriers. allow. for. controlled. biological.
properties.of.these.entities.for.the.timely.execution.of.therapeutic.and.diagnostic.func-
tions..Furthermore,.temporally.and.spatially.dependent.properties,.such.as.the.half-life.
of.the.carriers,.biodistribution,.local.physiological.stimuli.responsiveness,.and.the.abil-
ity. to. serve. as. imaging. and. contrast. agents. for. various. imaging. modalities. (magnetic.
