Biomedical Engineering Reference
In-Depth Information
nanoparticles. have. been. prepared. through. either. a. single. emulsion. or. double. emulsion.
method. (Rosca. et. al.. 2004).. For. the. single. emulsion. method,. hydrophobic. drugs. are.
dissolved. or. suspended. into. a. polymer. solution. via. a. water-immiscible,. volatile. organic.
solvent..Drug-loaded.organic.nanodroplets.are.then.formed.in.a.large.volume.of.water.in.
the.presence.of.an.emulsiier..The.solvent.in.the.emulsion.is.removed.by.either.evaporation.
or. extraction,. resulting. in. the. formation. of. nanoparticles.. The. double. emulsion. process.
is.similar.to.single. emulsion,. which. induces. the.formation.of.an.oil/water/oil. or.water/
oil/water. system.. Unlike. single. emulsion,. a. double. emulsion. method. is. usually. used. to.
encapsulate.hydrophilic.drugs.
A. typical. example. is. the. study. of. antiprostate. speciic. membrane. antigen. (PSMA).
aptamer-functionalized. poly(d,l-lactic-
co
-glycolic. acid)-
block
-poly(ethylene. glycol).
(PLGA-
b
-PEG). nanoparticles. (Farokhzad. et. al.. 2006,. Cheng. et. al.. 2007,. Zhang. et. al..
2007,. Dhar. et. al.. 2008).. The. aptamer. was. a. truncated. form. of. A10. RNA. aptamer. that.
was.developed.to.target.PSMA.overexpressed.prostate.cancer.cells..PLGA.and.PEG.are.
biocompatible. and. biodegradable. components. that. have. been. approved. by. the. Food.
and. Drug. Administration. (FDA). for. clinical. applications.. According. to. the. procedure,.
hydrophobic. drugs. were. irst. encapsulated. into. the. PLGA-
b
-PEG. nanoparticles..
Subsequently,. the. carboxyl. groups. on. the. surface. of. nanoparticles. were. activated. by.
EDC.and.sulfo-NHS..The.aptamers.bearing.primary.amino.groups.were.conjugated.to.
the.nanoparticles..An.MTT.assay.showed.that.the.aptamer-functionalized.nanoparticles.
were. more. cytotoxic. than. control. nanoparticles. (Farokhzad. et. al.. 2006).. Apart. from. in.
vitro. assay,. in. vivo. animal. studies. were. also. performed. to. evaluate. the. toxicity. of. this.
nanomaterial..The.results.indicated.that.aptamers.could.greatly.enhance.the.eficiency.
of.tumor.reduction.as.compared.to.control.nanoparticles.(Farokhzad.et.al..2006)..In.order.
to. increase. the. reproducibility,. another. method. was. developed. to. prepare. aptamer-
functionalized. nanoparticles. (Gu. et. al.. 2008).. In. this. procedure,. aptamers. were. irst.
conjugated. to. a. block. copolymer.. Drug. encapsulation. was. realized. by. self-assembly. of.
amphiphilic. triblock. copolymers. and. drugs.. The. attachment. of. aptamers. signiicantly.
enhances.the.cellular.uptake.of.nanoparticles.
Aptamers. have. also. been. used. to. functionalize. inorganic. nanoparticles.. Unlike.
organic.nanoparticles,.inorganic.nanoparticles.are.commonly.used.for.bioimaging.or.cell.
separation.purposes.(Chu.et.al..2006,.Herr.et.al..2006,.Bagalkot.et.al..2007,.Javier.et.al..2008,.
Wang.et.al..2008,.Pan.et.al..2010)..Recently,.quantum.dots.have.attracted.a.lot.of.attention.
because.of.their.high.photostabilities.and.narrow.emission.spectra.(Michalet.et.al..2005)..
Quantum.dots.are.semiconductor.nanocrystals.with.general.size.ranging.from.2.to.10.nm..
For. cell. recognition. applications. such. as. cancer. cell. imaging,. aptamers. were. grafted. to.
quantum.dots.(Chu.et.al..2006,.Bagalkot.et.al..2007)..There.are.two.approaches.to.attach.
aptamers.to.quantum.dots:.streptavidin-biotin.interaction.(Chu.et.al..2006).and.covalent.
bonding.(Bagalkot.et.al..2007)..In.the.former.approach,.biotinylated.aptamers.are.linked.to.
the.surface.of.quantum.dots.that.are.coated.with.streptavidin..The.latter.approach.relies.on.
EDC/NHS.activation..By.intercalation.Doxorubicin.(Dox).into.the.double-stranded.stem.of.
A10.aptamer.prior.to.the.conjugation,.researchers.have.explored.a.multifunctional.target.
delivery. system. that. combined. imaging,. therapy,. and. sensing. of. drug. delivery. together.
(Bagalkot.et.al..2007)..This.system.is.based.on.bi-luorescence.resonance.energy.transfer.
(FRET).mechanism..After.linking.with.Dox-containing.A10.aptamer,.the.luorescence.of.
quantum.dot.will.be.quenched.by.Dox..On.the.other.hand,.upon.binding.to.target.cells,.the.
Dox.will.be.released.from.the.complex..It.will.result.in.the.recovery.of.luorescent.signal.
from.quantum.dots.and.Dox..Besides.quantum.dots,.aptamers.can.also.be.conjugated.to.
contrast.agents.such.as.gold.nanoparticles.(Javier.et.al..2008).and.superparamagnetic.iron.
