Biomedical Engineering Reference
In-Depth Information
oxide. nanoparticles. (Wang. et. al.. 2008).. With. the. help. of. aptamers,. these. nanomaterials.
could.target.cancer.cells.speciically.
Aptamers. are. not. limited. to. conjugate. with. synthetic. nanoparticles.. In. 2009,. a. novel.
viral. capsid. DNA. aptamer. conjugate. was. developed. as. a. targeting. vehicle. (Tong. et. al..
2009)..A.genome-free.hollow.spherical.capsid.was.used.as.a.carrier..The.aptamers.were.
installed.on.the.surface.of.the.capsid.through.an.NaIO
4
-mediated.oxidative.coupling.strat-
egy.(Hooker.et.al..2006)..The.interior.of.the.capsid.was.luorescent.labeled.by.Alexa.Fluor.
488. through. standard. cysteine. bioconjugation.. The. functionalized. capsids. are. robust,.
nontoxic,.and.biodegradable.
2.3.3 Aptamer-Based Multifunctional Nucleic Acid Molecules
In.addition.to.the.studies.on.nucleic.acid.aptamer-functionalized.nanomaterials,.there.are.
other.promising.studies.that.take.advantage.of.the.unique.merits.of.nucleic.acid.molecules.
themselves..Single-stranded.oligonucleotides.have.inherent.lexibility,.which.allows.them.
to. fold. into. speciic. tertiary. structures. under. speciic. conditions.. In. addition,. these. lex-
ible.molecules.can.recognize.complementary.sequences,.resulting.in.the.formation.of.rela-
tively. rigid. structures.. Nucleic. acid. molecules. can. also. carry. genetic. codes. that. provide.
speciic.biological.functions.
Based.on.these.characteristics,.researchers.developed.a.bifunctional.nucleic.acid.molecule.
that.is.composed.of.an.aptamer.and.a.functional.nucleic.acid.tail.(Zhou.et.al..2009b)..The.
aptamer.was.an.anti-PTK7.DNA.aptamer.that.can.speciically.target.CCRF-CEM.cells..The.
tail.was.used.to.hybridize.a.short.complementary.sequence.which.carried.a.luorophore..
This.bifunctional.molecule.was.applied.to.develop.a.novel.pretargeting.system.(Figure.2.4).
(Zhou. et. al.. 2009b).. The. concept. of. pretargeting. is. twofold:. increasing. the. concentration.
of.drugs.in.target.sites.and.minimizing.their.side.effects.in.nontarget.organs..Therefore,.
the. large. bivalent. molecules. will. be. introduced. irst. to. target. speciic. cells.. Then. drug/
luorophore-equipped. complementary. sequences. will. be. introduced. to. the. system.
subsequently..Since.the.complementary.sequences.are.small,.they.can.rapidly.diffuse.into.
target. sites. to. bind. to. the. bivalent. molecules. and. can. also. be. quickly. cleared. from. the.
body..In.the.proof.of.concept.study,.in.vitro.experiments.were.performed.to.address.two.
questions:.whether.the.nucleic.acid.tail.affects.the.function.of.the.aptamer.and.whether.
the.complementary.sequence.can.recognize.the.nucleic.acid.tail.of.the.bivalent.molecule.
(Zhou.et.al..2009b)..The.results.showed.that.the.length.and.the.structure.of.the.nucleic.acid.
tail.were.two.key.factors.that.determined.the.pretargeting.eficiency..In.another.similar.
study,.a.trifunctional.molecule.was.studied..This.molecule.had.an.aptamer,.a.nucleic.acid.
tail,. and. a. reducing. agent. (DTT). (Mallikaratchy. et. al.. 2009).. The. short. complementary.
Bifunctional
molecule
Complementary
oligonucleotides
Figure 2.4
(See companion CD for color igure.)
.Schematic.representation.of.a.pretargeting.system.
