Biomedical Engineering Reference
In-Depth Information
when. they. are. exposed. in. a. nonideal. environment. due. to. their. fragile. functional. struc-
tures.. Therefore,. it. is. important. to. develop. synthetic. ligands. that. not. only. have. desired.
molecular.recognition.functions,.but.also.ones.that.can.endure.harsh.chemical.or.biological.
conditions..Nucleic.acid.aptamers.are.promising.synthetic.ligands.that.can.fulill.this.goal..
Representative.topics.using.aptamers.for.cell.recognition.are.described.in.the.following.
2.3.1 Aptamer-Based Synthetic Antibodies
Antibodies. have. been. widely. used. in. developing. material. systems. to. achieve. speciic.
cell. recognition. because. of. their. diversity. and. high. binding. afinity. (Ryan. et. al.. 1986,.
Schnittman.et.al..1989,.Asahara.et.al..1997,.Nagrath.et.al..2007)..Antibodies.can.be.attached.
to. chromatography. columns. and. used. to. bind. target. cells. (Ryan. et. al.. 1986).. Antibodies.
could.also.be.immobilized.on.magnetic.microbeads.(Asahara.et.al..1997).or.biochip.sur-
faces.(Nagrath.et.al..2007).to.isolate.target.cells.
Although. antibodies. have. a. lot. of. merits,. antibody-based. applications. are. often.
restricted. by. their. fragile. secondary. structures,. irreversible. denaturation,. and. limited.
shelf. half-lives.. In. practice,. the. applications. of. antibodies. are. generally. based. on. the.
conjugation. with. chemiluminescent. molecules. or. other. materials.. However,. during. the.
chemical.modiication.process,.it.is.very.challenging.to.control.the.chemical.reaction.sites.
on.antibodies..The.modiication.may.occur.in.the.variable.regions,.leading.to.the.loss.of.
their. binding. capabilities.. In. addition,. as. the. secondary. structures.of. natural. antibodies.
are. sensitive. to. environmental. conditions. such. as. temperature,. pH,. salts,. and. solvent.
(Reilly.et.al..1995,.Kozlowski.and.Swann.2006),.the.shelf.half-lives.of.antibodies.are.usually.
limited..Therefore,.it.is.of.great.interest.to.develop.new.nanomaterials.to.mimic.natural.
antibodies.
One. example. is. the. development. of. hybrid. aptamer-dendrimer. nanomaterials..
Dendrimers.are.well-deined.nanoscale.molecules.that.are.composed.of.multiple.identical.
branches.extended.from.a.central.core.(Lee.et.al..2005b)..Compared.to.conventional.linear.
polymers,.dendrimers.are.multivalent.and.monodispersed..Therefore,.dendrimer-based.
nanomaterials. are. of. widespread. interest. for. many. applications. such. as. drug. delivery.
(Bielinska.et.al..2000),.gene.delivery.(Wimmer.et.al..2002),.tissue.sealants.(Carnahan.et.al..
2002),. and. molecular. encapsulation. (Hawker. et. al.. 1993).. Because. of. the. multivalency,.
dendrimers.have.been.widely.used.in.chemical.modiications..The.large.number.of.surface.
groups.allows.a.great.opportunity.for.further.conjugation.with.other.molecules,.such.as.
targeting.molecules,.luorophore,.or.even.drugs..Besides.the.high.degree.of.branching.for.
surface.conjugation,.the.cavities.inside.the.dendrimers.can.be.used.to.encapsulate.a.large.
quantity. of. small. particles,. such. as. drugs. (Morgan. et. al.. 2006). or. metal. nanoparticles.
(Crooks. et. al.. 2001,. Boisselier. et. al.. 2010).. Overall,. all. these. advanced. features. make.
dendrimers.a.promising.scaffold.to.provide.deined.conjugation.sites.for.further.chemical.
modiication..Zhou.et.al..were.the.irst.to.utilize.nucleic.acid.aptamers.and.dendrimers.
to. build. hybrid. aptamer-dendrimer. nanomaterials. for. targeted. cell. labeling. (Zhou.
et. al.. 2009a).. In. this. research,. a. DNA. aptamer. sgc8c. that. was. selected. against. a. human.
T. lymphocytic. leukemia. cell. line. CCRF-CEM. was. conjugated. to. a. poly(amidoamine).
(PAMAM).dendrimer..The.chemical.conjugation.was.based.on.the.formation.of.a.stable.
amide.bond..In.brief,.a.generation.5.PAMAM.dendrimer.with.128.carboxyl.groups.on.the.
surface. was. activated. by. dicyclohexylcarbodiimide. (DCC). and. N-hydroxysuccinimide.
(NHS). to. form. NHS. ester.. The. activated. dendrimers. were. reacted. with. sgc8c. aptamer,.
which. had. a. primary. amino. group. at. the. 5′. end.. Fluorescein. cadaverine. (FC). was.
also. conjugated. to. the. PAMAM. dendrimer. to. provide. luorescent. signal.. The. binding.
