Nanotoxicity - The Nanobiotechnology - page 610

and.peroxides..Many.in.vivo.and.in.vitro.toxicology.studies.conirm.that.for.low.solubility,.
low.toxicity.materials.such.as.SiO 2 ,.TiO 2 ,.and.carbon.black,.ultraine.particles.are.more.toxic.
and.inlammogenic.than.ine.particles..The.nanoparticles.generate.ROS.to.a.greater.extent.
than.larger.particles.leading.to.increased.transcription.of.pro-inlammatory.mediators.via.
intracellular.oxidative.stress..ROS.can.be.generated.from.the.surface.of.particles.such.as.iron,.
lead,.cadmium,.silver,.nickel,.vanadium,.chromium,.manganese,.and.copper.nanoparticles.
that. are. capable. of. catalyzing. Fenton's. reaction. (Li. et. al.. 2003,. He. et. al.. 2011).. This. means.
that.ROS.can.be.generated.where.nanoparticles.reside.and.exist.by.the.direct.interactions.
between.nanoparticles.and.biomolecules.in.the.cells..Following.the.induction.of.ROS,.cellular.
antioxidants.will.be.greatly.decreased..The.DNA,.protein,.and.cellular.organelles.are.easily.
damaged.consequently..The.ROS.may.also.activate.the.MAPK.or.NF-κB.signal.transduction.
pathway. and. trigger. the. high. expression. of. inlammation. related. markers. such. as. IL-1,.
IL-6,.IL-8,.TNF-a.(Park.et.al..2008,.Muller.et.al..2010,.Moon.et.al..2010)..Over.production.of.
ROS. induces. mitochondrial. membrane. permeability,. damages. the. respiratory. chain,. and.
triggers.the.apoptotic.process..Oxidant.stress.broadly.deines.the.redox.state.achieved.when.
there. is. an. imbalance. between. antioxidant. capacity. and. ROS.. Cell-speciic. cytotoxicity. of.
nanomaterials. has. been. found. in. various. nanobiotechnology. applications.. In. our. lab,. we.
have.observed.that.Au.nanorods.have.distinct.effects.on.cell.viability.by.killing.cancer.cells.
while. posing. negligible. impact. on. normal. cells. and. mesenchymal. stem. cells.. The. basic.
mechanism. may. come. from. intracellular. localization,. not. via. an. uptake. pathway,. which.
determines.the.inal.fate.of.both.Au.nanorods.and.cells..Due.to.the.enhanced.permeation.
of. the. lysosomal. membrane. after. Au. nanorod. uptake,. Au. nanorods. are. released. into. the.
cytoplasm. of. cancer. cells. and. translocated. from. endosomes/lysosomes. to. mitochondria,.
inducing. decreased. mitochondrial. membrane. potentials,. increased. ROS. levels,. oxidative.
stress.and.inally,.reduced.cell.viability..However,.Au.nanorods.show.almost.no.toxicity.in.
normal.cells.and.mesenchymal.stem.cells.since.their.lysosomal.membranes.remain.more.
intact.(Qiu.et.al..2010,.Wang.et.al..2011)..On.the.other.hand,.some.nanomaterials.will.show.
absolute. acceptable. characteristics. in. vivo.. For. example,. various. water. soluble. fullerenes.
and. its. derivatives. are. potent. antioxidants. and. help. to. prevent. the. overproduction. of.
mitochondrial.ROS.(Lao.et.al..2009,.Yin.et.al..2009,.Jiao.et.al..2010)..Recently,.we.found.a.bis-
adduct.malonic.acid.derivative.of.fullerene,.C 60 (C(COOH) 2 ) 2 ,.which.inhibits.tumor.necrosis.
factor. alpha-initiated. cellular. apoptosis. by. stabilizing. lysosomes. and. up-regulating. the.
expression.of.Hsp.70.(Li.et.al..2011)..Metallofullerene.nanoparticles.[Gd@C 82 (OH) 22 ] n .did.not.
show. signiicant. side. effects. in. vivo;. they. can. overcome. tumor. resistance. to. cisplatin. by.
increasing. its. intracellular. accumulation. through. the. restoration. of. defective. endocytosis..
This.inding.can.be.extended.to.other.challenges.related.to.multidrug.resistance.often.found.
in.cancer.treatments.(Liang.et.al..2010).
The. molecular. mechanisms. of. the. adverse. effects. of. nanoparticles. including. SWCNTs,.
semiconductor.QDs,.nano-copper,.and.cerium.oxide.have.been.reported,.and.the.proposed.
inlammatory.mechanism.is.summarized.in.Figure.27.6.(Chan.et.al..2006,.Long.et.al..2006,.
Li.et.al..2007,.Park.et.al..2008,.Zhang.et.al..2012)..Overall,.the.results.imply.that.the.special.
physicochemical. characteristics. of. nanoparticles. not. only. produce. more. serious. biological.
effects.to.the.lungs,.but.also.show.different.cytokinetic.behaviors.that.cause.a.prolonged.clear-
ance.at.a.level.below.the.volumetric.particle.overload.and.increase.inlammatory.responses.
27.4.2 Cardiovascular System
Epidemiologic. evidence. shows. that. the. presence. of. ultraine. particulate. air. pollution. is.
associated. with. cardiovascular. diseases. and. myocardial. infarction.. It. could. likely. be.