Biomedical Engineering Reference
In-Depth Information
nanoparticle,. the. native. hydrated. iron. oxide. is. removed. by. acidic. dialysis,. and. then. apo-
ferritin. is. reconstituted. by. Fe(II). under. slow. oxidative. conditions. at. 600°C. and. pH. 8.5.
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.
Magnetoferritin.particles.are.cleared.rapidly.from.the.blood.by.the.liver,.spleen,.and.lymph.
nodes.
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Oxidation.of.Fe(II).at.slightly.elevated.pH.and.temperature.forms.a.highly.soluble.nano-
composite.of.iron.oxides.and.dendrimers.and.was.described.by.Bulte.et.al..as.a.class.of.
magnetic. contrast. agent. designed. to. achieve. a. high. degree. of. nonspeciic. intracellular.
magnetic. labeling. for. any. mammalian. cell,. including. human. stem. cells.
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. These. aggre-
gates.have.an.overall.size.of.20-30.nm,.and.labeled.oligodendroglial.progenitors.can.be.
readily.detected.in.vivo.as.long.as.6.weeks.after.transplantation..Similarly,.liposomes,.the.
drug. and. gene. delivery. agents,. were. used. as. a. coating. material. to. solubilize. iron. oxide.
nanoparticles. by. Bulte. and. co-workers.
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. Liposomes. have. the. same. bilayer. structure. as.
cell. membrane. and. are. made. up. of. surfactant. molecules. with. a. hydrophilic. head. and. a.
hydrophobic. tail. that. can. be. illed. with. iron. oxide.. The. magnetoliposome. core. size. and.
total. size. are. 16. and. 40. nm,. respectively,. and. were. used. for. successfully. tracking. bone.
marrow.stem.cells.
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In.contrast.to.conventional.iron.oxide.nanoparticles.that.are.taken.up.by.the.reticulum.
endoplasmic.system.(RES).rapidly,.particles.that.are.made.via.a.nonhydrolytic,.high-tem-
perature.growth.method.are.able.to.escape.from.RES,.and.possess.an.active.functional.site.
to.link.with.biological.active.molecules.
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.However,.as.nonhydrolytically.synthesized.mol-
ecules,.they.are.soluble.only.in.organic.media.and.need.surface.modiication,.including.a.
bifunctional.ligand,
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.micellular,
213,214
.polymer,
215
.and.siloxane.linking.procedure,
216,217
.
to.be.water-soluble.nanoparticles..Nitin.and.co-workers.developed.functionalized.super-
paramagnetic.iron.oxide.nanoparticles.with.a.polyethylene.glycol.(PEG)-modiied.coating,.
leading.to.high.water.solubility.and.stability,.and.allowing.for.bioconjugation.of.various.
moieties,.including.luorescent.dyes.and.the.Tat.peptide.
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.The.PEGylated.nanoparticles.
were.delivered.into.living.cells.for.further.study.by.using.MRI.
Polymeric. phosphine. oxide. binds. tightly. to. iron. oxide. nanoparticle. surfaces. through.
multidendate.bondings..Kim.and.co-workers.brought.a.variety.of.nanoparticles.into.water.
using.easily.synthesized.polymers.consisting.of.phosphine.oxide.and.PEG.
218
.Since.high.
iron. concentrations. intensify. high. T1-weighted. and. low. T2-weighted. signals,. in. spite. of.
conventional.iron.oxide.nanoparticles,.the.phosphine-stabilized.γFe
2
O
3
.particles.are.potent.
T1.and.T2.relaxation.agents..Similarly,.2,3-dimercaptosuccinic.acid.(DMSA).ligands.have.
been. used. to. produce. water-soluble. iron. oxide. (WSIO). nanoparticles,. which. are. able. to.
bind.to.target-speciic.biomolecules.through.the.remaining.free.thiol.group.of.the.ligand.
200
.
These.nanoparticles,.upon.conjugation.with.Herceptin,.known.as.a.cancer-targeting.anti-
body,.have.been.used.for.in.vitro.and.in.vivo.cancer.cell.imaging.
200,212
The. particle. entrance. into. a. cell. or. a. particle's. link. with. other. biological. molecules. is.
essential.for.cell.labeling..Superparamagnetic.nanoparticles'.internalization.as.nanoparti-
cles.depends.on.speciic.transmembrane.mechanisms,.which.we.have.discussed.before.for.
quantum.dots..Phagocytosis,.receptor-mediated.endocytosis,.and.pinocytosis.are.the.main.
mechanisms.for.supernanoparticle.cell.entrance..However,.the.coating.design.can.control.
the.internalization.rate.and.provide.the.optimum.timing.for.MRI.contrast.agents.
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.Speciic.
surface. receptors. are. used. to. facilitate. labeling. of. the. cells. without. phagocyte. capacity..
Monoclonal. antibodies. for. speciic. proteins. or. receptors,. nanoparticle. surface. modiiers.
such. as. magnetodendrimers,. and. surface. charge. modiiers. such. as. anionic. maghemite.
nanoparticles.are.the.most.used.protocols.for.receptor-mediated.labeling.
Although. transfection. agents,. which. are. highly. charged. macromolecules. to. intro-
duce.DNA.into.cells,.are.toxic.to.cells,.poly-L-ornithine,
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.poly-L-lysine,
221
.and.HIV-1.Tat.
