Quercetin Attenuates Neurotoxicity Induced Los Ntawm Hlau Oxide Nanoparticles Part 2

Thov hu rauoscar.xiao@wecistanche.comyog xav paub ntxiv

Hlau nyob rau hauv cov kab mob dementia-associated Hlau thiab Alzheimer's kab mob

AD yog ib qho kev mob hlwb uas maj mam rhuav tshem kev kawm, kev nco, thiab kev txawj xav. Hnub nyoog, poj niam txiv neej, muaj kev cuam tshuam ntawm caj ces, txoj kev ua neej, thiab ntau yam kab mob xws li ntshav qab zib thiab mob hlab ntsha tawg nrog rau lub hlwb hlau tsub zuj zuj yog qhov muaj feem cuam tshuam txog AD [87, 88]. Senile plaques muaj aggregates ntawm extracellular amyloid-beta (A) oligomers thiab neurofibrillary tangles (NFTs) muaj aggregates ntawm intracellular txawv txav.hyperphosphorylatedtau protein yog ob hom kab mob pathological ntawm AD. Muaj kev sib raug zoo ntawm cov hlau tsub zuj zuj thiabpathological yam ntxwvntawm AD. Qhov txawv txav ntawm cov hlau nyob rau hauv hippocampus thiab cortex ntawm AD- cuam tshuam cov kev kawm tau raug tshaj tawm 75]. Ib qho kev tshawb fawb hauv vivo qhia tau hais tias cov hlau deposits nrog cov plaques senile nyob rau hauv lub hlwb ntawm ib tug transgenic nas qauv ntawm AD los ntawm quantitative susceptibility mapping (QSM), cov txheej txheem tshiab hauv MRI [89]. Cov plaques thaum ntxov tau tsim nyob rau hauv parallel nrog hlau overload nyob rau hauv tus nas qauv ntawm AD [90]. Fe ntxiv nyob rau hauv senile plaques

tuaj yeem hloov mus rau ntau hom hlau, Fe2 ntxiv, los ntawm A [78]. Ntawm qhov tod tes, 4-HNE tau tsa los ntawm lipidperoxidationncaj qha reacts nrog A thiab tsim cov khoom oxidation, uas ua rau A aggregation [76]. Tsis tas li ntawd, A peptide ncaj qha tsim H, O, nyob rau hauv ib qho kev txo qis-nyob ntawm cov hlau, txheej txheem uas exacerbates oxidative kev nyuaj siab thiab hlau overload [91]. Hlau tuaj yeem nce qhov kev qhia ntawm amyloid precursor protein (APP) los ntawm kev cuam tshuam rau IRE qhov chaw ntawm APP mRNA. Tsis tas li ntawd, hlau tuaj yeem khi rau A thiab nce A aggregation 92]. Kev sib raug zoo ntawm hlau deposition thiab tau phosphorylation tau pom los ntawm cortical imaging los ntawm QSM thiab tau Positron Emission Tomography scanning (tau-PET) hauv AD subjects [93]. Hlau txhawb cov phosphorylation ntawm tau los ntawm kev ua kom lub cyclin-dependent kinase (CDK5) / P25 complex thiabglycogensynthase kinase-3 (GSK-3 ) tsim NFTs thiab txo cov eflux ntawm hlau ions[92]. Raws li cov lus piav qhia no, nws tuaj yeem xaus lus tias muaj kev tawm tswv yim zoo ntawm cov hlau tsub zuj zuj, oxidative kev nyuaj siab, A aggregation, thiab tau hyperphosphorylation. Cov kws tshawb fawb tuaj yeem txo cov tshuaj lom ntawm cov plaques, txhim kho cov solubility ntawm A, thiab txo qhov tsim ntawm NFTs los ntawm kev tshem tawm cov hlau ions los ntawm kev siv hlau chelators.

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Thov nias ntawm no kom paub ntxiv

Hlau thiab Parkinson tus kab mob

PD yog lwm tus kab mob neurodegenerative uas muaj cov tsos mob ntawm lub cev muaj zog. Kev paub txog kev poob qis feem ntau tshwm sim ob xyoo caum ua ntej kev kuaj mob ntawm lub cev muaj zog. Yog li ntawd, kev kuaj mob ntxov nrog kev xav txog kev poob qis tuaj yeem tiv thaiv qhov kev loj hlob ntawm PD[94]. PD tshwm sim vim qhov degeneration ntawmdopamine neuronstshwj xeeb tshaj yog nyob rau hauv ib feem ntawm cov substantia nigra hu ua pars compacta. Considerably, qhov poob ntawm dopamine

nyob rau hauv lub pars compacta cuam tshuam kev yeem lub cev muaj zog tswj, nce tag nrho excitatory tsav nyob rau hauv lub basalganglia, thiab ua rau cov tsos mob ntawm PD. Tsis pub dhau lub synapse, dopamine tuaj yeem tawg thiab tsis ua haujlwm los ntawm ob lub enzymes suav nrog monoamine oxidase (MAO) thiab catechol-O-methyl transferase (COMT) [95]. MAO kev ua haujlwm tau paub tias cuam tshuam rau cov hlau lev-els hauv cov tsiaj thiab tib neeg. Muaj kev sib cuam tshuam ntawm cov qib hlau dawb thiab MAO hauv lub hlwb. Txawm li cas los xij, nce oxidative kev ntxhov siab zoo li yog qhov sib txuas ntawm MAO, qib hlau, thiab kev puas tsuaj rau neuronal. H, O2 yog ib yam khoom ntawm monoamine oxidation ntawm MAO. H, O, tuaj yeem koom nrog Fenton cov tshuaj tiv thaiv thiab tsim cov dawb radicals uas muaj zog heev. Hauv kev laus, MAO thiab lub hlwb hlau qib nce ntxiv uas ua rau muaj kev nce hauv cov tshuaj tiv thaiv Fenton thiab kev puas tsuaj ntawm macromolecules [96]. Yog li inhibition ntawm MAO lossis tshem tawm ntawm Fe²ions los ntawm cov hlau chelator yog ob txoj hauv kev nrog tib lub hom phiaj hauv PD cov neeg mob tib lub sijhawm, nce qib monoamine, txo cov khoom ntawm Fenton cov tshuaj tiv thaiv, thiab qhov tshwm sim oxidative kev nyuaj siab.

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Cistanche tuaj yeem txhim kho kev tiv thaiv

Zoo li AD, hyperphosphorylated tau thiab txo qis hauv soluble tau tuaj yeem ua rau cov hlau ntau dhau hauv cov neurons los ntawm kev txo qis hauv APP-mediated hlau xa tawm, uas tej zaum yuav yog ib qho ua rau nco tsis ua haujlwm hauv PD [97]. Tsis tas li ntawd, hlau deposition tau pom nyob rau hauv cov qauv txhawb kev txawj ntse xws li hippocampus [85]. Cov pov thawj sau los ntawm 1988 txog 2008 los ntawm A Jon Stoessl li al. pom qhov txawv txav ntawm cov hlau, uas feem ntau yog ua ke nrog ferritin hauv substantia nigra neurons, lub cev muaj zog ntawm cov neeg mob PD. Cov ntaub ntawv no qhia tau hais tias hlau concentration yog ncaj qha ntsig txog qhov mob ntawm tus kab mob [98]. Lewy lub cev thiab Lewy neurites muaj xws li txawv txav a-Synuclein filaments yog qhov tseem ceeb tshaj plaws neuropathological yam ntxwv ntawm PD [94]. Ntawm qib molecular, muaj kev sib raug zoo ntawm a-Synuclein aggregation thiab hlau tsub zuj zuj. Fe3 ntxiv los ntawm Fenton cov tshuaj tiv thaiv ncaj qha induces a-synuclein qhia thiab aggregation. Overexpression ntawm hepcidin, ib tug muaj peev xwm regulator ntawm hlau transporters, txo cov tsub zuj zuj ntawm hlau nyob rau hauv lub hlwb thiab Fenton cov tshuaj tiv thaiv yog li ib tug-Synuclein aggregation thiab ROS ntau lawm yog txo nyob rau hauv lub high-kev pheej hmoo ntawm lub hlwb muaj feem xyuam rau dementia thiab lub cev muaj zog teeb meem [99, 100]. Yog li daim ntawv thov ntawm cov hlau chelators uas txhim kho qhov kev qhia ntawm hepcidin tuaj yeem inhibit a-synuclein aggregation.

Hlau thiab mob stroke

Muaj pov thawj rau crosstalk ntawm qee hom mob stroke, hlau overload, thiab nco tsis ua haujlwm [86, 101, 102]. Stroke yog ib qho ntawm cov laj thawj tseem ceeb ntawm kev nco tsis ua haujlwm, thiab ze li 30 feem pua ntawm cov neeg mob stroke tsim dementia nyob rau hauv 1 xyoo ntawm mob stroke pib [103]. Athero-sclerosis, ntshav qab zib, ntshav siab, haus luam yeeb, siab BMI, thiab dyslipidemia yog qhov pheej hmoo rau ischemic stroke [104]. Ob peb lub tswv yim koom nrog hauv kev raug mob ntawm lub hlwb vim yog mob ischemia nrog rau kev mob, oxidative kev nyuaj siab, nce siab ntawm calcium intracellular, txhim kho excitatory amino acids, thiab nce qib ntawm cov hlau dawb thiab ferritin [105]. Post-stroke memory dysfunction kuj tuaj yeem tshwm sim los ntawm vascular dementia, AD pathology [103], hlau overload, thiab oxidative stress [86]. Edema tsim los ntawm cov hlau ntau dhau ua rau oxidative cell puas tom qab hemorrhagic stroke [106]. Hlau deposition nrog los ntawm kev txo qis hauv GSH thiab GPX thiab nce hauv lipid peroxidation tau tshaj tawm hauv cov neurons ntawm ischemic stroke qauv [83]. Kondo thiab al.reported hlau deposition nyob rau hauv lub hippocampus, striatum, thiab cerebral cortex nyob rau hauv nas nrog ib ntus forebrain ischemia. lig thiab ntxov lipid peroxidation vim hlau deposition tom qab ischemia tej zaum yuav yog ib qho ntawm cov ua rau neuronal cell tuag [107]. Tsawg oxygen mob tshwm sim los ntawm ischemic stroke ua rau muaj hlau ntau nkag mus rau hauv lub hlwb. Ntawm qhov tod tes, acidic pH tshwm sim los ntawm ischemic stroke ua rau dissociation ntawm Fe3 los ntawm transferrin thiab nws txo mus rau Fe2 ntxiv, yog li NTBI uptake tshwm sim. Neurons uptake NTBI thiab undergo Fenton / Haber-Weiss cov tshuaj tiv thaiv, uas tsim teeb meem reactive radicals hom thiab ua rau lipid peroxidation thiab neuronal cell tuag [55].

IONPs metabolism-induced neurotoxicity

IONPs muaj cov hlau oxide core thiab txheej tiv thaiv [108, 109]. Hlau oxides muaj ntau yam tshuaj xws li magnetite (Fe, O)), maghemite y-Fe, O3), hematite (a-Fe, O:), thiab wustite (FeO) [108]. Ntawm lawv, Fe, Av Y-Fe, O, yog siv dav hauv nanomedicine [14]. Txawm hais tias qhov zoo sib xws ntawm ob cov hlau oxides no, Fe, O, yog cov hlau nplaum ntau dua thiab tsis ruaj khov dua li y-Fe, O, [110].Bare IONPs khaws cia thaum nkag mus rau hauv kev ncig vim muaj kev cuam tshuam ntawm lawv tus kheej. IONPs tsub zuj zuj txhawb lub cev tiv thaiv kab mob yog li IONPs tuaj yeem raug rhuav tshem hauv kev ua haujlwm ntawm opsonization-dependent mechanism.

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Yog li, cov txheej txheem tiv thaiv zoo li tsim nyog rau kev ua kom zoo ntawm IONPs nrog rau kev ruaj ntseg, biocompatibility, multi-functionalization, optimal biodegradation, hydrophilic interactions, thiab solubility [109]. Ob hom IONPs feem ntau yog siv rau nanomedicine: superparamagnetic hlau oxide nanoparticles (SPIONs) nrog ib txoj kab uas hla ntawm 50-100 nm thiab ultra-me me superparamagnetic hlau-oxide nanoparticles (USPIONs) nrog txoj kab uas hla mus txog 50 nm [lll] . IONPs tuaj yeem nkag mus rau tib neeg lub cev los ntawm ntau txoj kev tswj hwm suav nrog kev txhaj tshuaj (IV), intramuscular (IM), subcutaneous, intrathecal, intra-tumoral, qhov ncauj, thiab qhov ntswg. Ob peb lub tswv yim yog npaj rau IONPs uptake los ntawm cov hlwb xws li passive diffusion, phagocytosis, thiab hom endocytosis txawm nyob los yog ywj siab los ntawm clathrin thiab caveolae [112]. Txoj kev nkag ntawm IONPs mus rau hauv lub xovtooj yog nyob ntawm lawv cov khoom siv physicochemical xws li qhov loj, zoo li, hom txheej, thiab kev ua haujlwm ntawm cov khoom no[113-115]. IONPs muaj ib tug nanoscale loj thiab siab saum npoo-rau-mass piv. Txawm hais tias yog qhov zoo dua, cov khoom no tuaj yeem ua rau muaj kev cuam tshuam ntau dua thiab cytotoxicity [116]. Ntau qhov kev tshawb fawb tau ua tiav ntawm qhov ua tau ntawm IONPs toxicity hauv ntau cov ntaub so ntswg, tshwj xeeb tshaj yog cov hlwb neural. Txawm hais tias tab tom txhim kho kev nco tsis zoo, lawv lub luag haujlwm txheeb ze hauv neurodegeneration thiab exacerbating memory disorders tau tham me ntsis. Cytotoxicity ntawm IONPs nyob ntawm physicochemical zog xws li qhov loj me, cov duab, hom txheej, tus nqi saum npoo, raug lub sij hawm / concentration, pab pawg ua haujlwm, thiab hom cell kho nrog IONPs [14, 117]. Tsis tas li ntawd, nws tau raug tshaj tawm tias lub xeev oxidation ntawm Fe ions hauv cov hlau oxide core txiav txim siab cytotoxicity ntawm IONPs. Fe; O4 vim muaj peev xwm oxidation tau pom ntau dua genotoxicity tshaj y-Fe, O, hauv A549 tib neeg lub ntsws epithelial cell [112]. Txawm hais tias, pov thawj los ntawm ntau qhov kev tshawb fawb qhia tias IONPs uas muaj Fe, O2core muaj cov tshuaj toxicity qis dua piv nrog y-Fe, O, vim lawv tshem tawm sai ntawm lub cev [14,118]. Feem ntau, qhov loj ntawm IONPs toxicity yog cov hlau ions. tso tawm los ntawm lub hauv paus [119] Cov hlau ions no nrog rau lwm cov khoom los ntawm IONPs metabolism tuaj yeem cuam tshuam nrog hlau homeostasis. Hauv vivo cov kev tshawb fawb tau qhia tias daim siab ferritin qib tau txhim kho tom qab IONPs kev kho mob, qhia tias IONPs degraded, thiab lawv cov khoom metabolic induced alterations ntawm hlau teb [120, 121]. IONPs dhau los ntawm BBB los ntawm internalization mechanisms los yog kev puas tsuaj ntawm endothelial cell membranes [14]. Hlau uptake uas tshwm sim los ntawm NPS metabolism nyob ntawm theem ntawm TfR qhia rau ntawm tes [122]. IONPs tau tshaj tawm tias hla BBB los ntawm kev cuam tshuam nrog TfR ntawm lub abluminal membrane ntawm endothelial hlwb. Tsis tas li ntawd, kev cuam tshuam BBB thiab ROS txhim kho los ntawm kev raug 10 ug / ml ntawm Fe-NPs (10 thiab 30 nm) rau 24 teev hauv cov khoom siv BBBs tau tshaj tawm [121]. Hauv qhov no, Jain et al. qhia tias IV kev tswj hwm ntawm MNP (10 mg ntawm Fe / kg hauv 100 μL ntawm saline) nyob rau hauv lub sij hawm ua ntej cov ntsiab lus tsis hloov cov qib ntawm cov hlau nyob rau hauv nas hlwb. Thaum lub sij hawm, kev khi ntawm cov tso tawm hlau-transferrin complex rau TfR ntawm BBB ua rau muaj kev nce hauv cov ntsiab lus hlau ntawm lub hlwb, tshwj xeeb tshaj yog ib lub lim tiam tom qab txhaj tshuaj MNP [122]. Yog li, theem ntawm TfR qhia ntawm lub xov tooj ntawm tes yog lwm yam uas txawv NP uptake. Tom qab lub internalization ntawm IONPs nyob rau hauv lub cell, lawv muab tso rau hauv lub acidic ib puag ncig ntawm lub lysosome thiab metabolized ua rau tso tawm ntawm dawb hlau ions mus rau hauv lub cytosol. Qhov kev puas tsuaj no pib los ntawm qhov chaw ntawm NPs thiab maj mam txuas mus rau lawv lub hauv paus. Cov ions tso tawm tuaj yeem koom nrog Fenton / Haber-Weiss cov tshuaj tiv thaiv. Cov txiaj ntsig ntawm qhov kev tshwm sim no yog tshwm sim los ntawm cov tiam ntawm cov khoom oxidation thaum ntxov thiab theem nrab uas tuaj yeem ua rau cov cellular Cheebtsam xws li nucleic acids, proteins, lipids, mitochondria [112, 123], thiab thaum kawg ua rau apoptosis [14,124]. Yog li, nws muaj pov thawj tias CNS tuaj yeem cuam tshuam los ntawm IONPs. Cov xwm txheej no yog qee yam cuam tshuam nrog neurodegeneration [121]. Thaum lub sij hawm cov kab mob neurodegenerative uas BBB tau dhau los ua rau ntau lub ntsiab lus, tshwj xeeb tshaj yog NPS, kev siv IONPs tuaj yeem ua rau tus kab mob hnyav dua [14]. Muaj pov thawj ntawm NPs toxicity hauv cov kab mob dementia xws li AD, PD[121], thiab mob stroke|125|.In vitro qauv ntawm AD qhia tias hlau oxide-based NPs tuaj yeem ua rau mob hnyav los ntawm kev tsim cov complexes nrog A [126]. C-Abl tyrosine kinase plays lub luag haujlwm tseem ceeb hauv kev tuag ntawm cov hlwb hauv PD. Kev ua kom c-Abl, nce -synuclein, txo cellular proliferation, nce ROS, thiab mitochondrial permeability tau tshaj tawm nyob rau hauv neurons tom qab SPIONs kho los ntawm Imam li al. [121] .Leakage ntawm electrons mus rau cytosol vim mitochondrial permeability ua rau txo qis ntawm striatal dopaminergic neurons hauv nas [121].Iron depositions induced los ntawm IV txhaj tshuaj USPIONs [2 mmol hlau / kg lub cev hnyav (0.15 ml)] muaj tau pom nyob rau hauv tus qauv mob stroke nas. Nws kuj tau pom tias USPIONs tuaj yeem nkag mus rau lub hlwb parenchyma thiab CSF los ntawm kev hla BBB, uas tau pom los ntawm kev tshawb pom ntawm USPIONs hauv meningeal macrophages thiab phagocytes hauv CSF-bathed thaj chaw [125].

Hlau concentration hauv lub hlwb tsis zoo li qub thiab cuam tshuam los ntawm ntau yam xws li hnub nyoog, kev noj zaub mov tsis zoo, tsis muaj hlau tsis txaus, thiab muaj hlau ntau dhau. Cov ntsiab lus hlau ntawm cov cheeb tsam sib txawv ntawm lub hlwb sib txawv. Macro divisionally cov teeb meem dawb muaj ntau dua concentration ntawm hlau. Hauv zos divisionally, globus pallidus, liab nucleus, substantia nigra, caudate-putamen, thiab dentate nucleus muaj ntau dua cov hlau [l27]. Ntau qhov kev tshawb fawb tau tshuaj xyuas cov ntaub so ntswg ntawm IONPs hauv lub hlwb. Tsis tas li ntawd, muaj pov thawj rau toxicity induced los ntawm coated IONPs. Kev tswj hwm IV nquag ntawm ferumoxytol (8 mg / kg) ua cov khoom hloov hlau rau 4 lub lis piam hauv cov nas pom tias IONP tuaj yeem ua rau cov hlau tsub zuj zuj hauv cov hlab ntsha. Hlau concentration hloov lub sij hawm raug xam los ntawm QSM txheej txheem. Kev hloov me ntsis ntawm cov ntsiab lus hlau nyob rau hauv striatum thiab corpus callosum tau tshaj tawm los ntawm kev siv thaj tsam ntawm kev txaus siab (ROI), uas tej zaum yuav cuam tshuam nrog cov hlau tso rau hauv lub hlwb parenchyma. Tsis tas li ntawd, qhov kev ntsuam xyuas histopathological tau pom choroid plexus hemosiderosis thiab midbrain vacuolation nyob rau hauv lub hlwb parenchyma [128].

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Hauv kev tshawb fawb hauv vivo, radiolabeled aminopropyltriethox-ysilane (APTS)-coated IONPs tau instilled intranasally hauv Sprague Dawley nas nyob rau hauv ib qho concentration ntawm 10 ug (hauv 10 ul). IONPs concentration hauv cov cheeb tsam hauv cheeb tsam nyob rau hnub xya ntawm kev raug raug ntsuas. Lub olfactory noob, stria-tum, hippocampus, hlwb qia, cerebellum, thiab frontal cortex pom qhov siab tshaj plaws concentration ntawm IONP depositions, feem. Txawm tias ntau tshaj 50 feem pua ntawm IONP tseem nyob hauv striatum thiab hippocampus los ntawm 14 hnub tom qab. Tsis tas li ntawd, kev puas tsuaj oxidative nce hauv stria-tum thiab hippocampus. Tom qab nyob rau hauv vivo txoj kev tshawb fawb, toxicity mechanisms raug ntxias los ntawm IONP tau tshawb xyuas hauv dopaminergic neuronal PC12 hlwb. Incubated PC12 hlwb nrog IONPs (100 thiab 200 mg / ml) pom cytotoxicity tseem ceeb nrog rau qib MDA siab thiab txo qis ntawm GSH-PX thiab SOD. Tawm PC12 hlwb kuj tau pom qhov nce hauv phosphorylation ntawm c-Jun, JNK, thiab p53, uas tau cuam tshuam nrog oxidative kev nyuaj siab thiab kev tuag ntawm tes [129]. Rau qhov zoo tshaj plaws ntawm peb txoj kev paub, tsis muaj qee qhov kev tso cai siab tshaj plaws ntawm IONPs hauv ntau qhov chaw ntawm lub hlwb. Qhov no txawv rau IONPs thiab nyob ntawm physicochemical zog thiab standardization.

IONPs nto txheej

Nws yog qhov paub zoo tias kev ua kom zoo tshaj plaws ntawm lub cev tsis zoo ntawm IONPs yog qhov ua tau zoo los txo qis kev cuam tshuam ntawm cov NPs thiab cov hlwb, tiv thaiv kab mob, thiab tshuaj lom. Thaum twg ib qho nanoparticle tshiab tau tsim, ib qho ntawm thawj yam tseem ceeb uas yuav tsum tau xav txog yog nws cov txheej txheej. Lub txheej khaws cia lub hauv paus ntawm nanoparticles thiab tiv thaiv kev tso tawm ntawm nanoparticles. Txawm li cas los xij, txheej nws tus kheej yuav tsum tsis txhob muaj tshuaj lom. Ib txoj hauv kev los txo cov toxicity ntawm nanoparticles yog los npog lawv. Txheej nanoparticles, ntxiv rau ua rau lawv siv tau thiab txo lawv cov toxicity, kuj ua rau lawv muaj txiaj ntsig [6]. Nyob ntawm hom thiab daim ntawv thov ntawm nanoparticles, ntau hom txheej tau siv. Qee cov coatings yog siv los tiv thaiv nanoparticles los ntawm kev hloov pauv hauv plab hnyuv, thiab qee qhov yog siv los sib txuas mate-rials rau hauv nanoparticles. Nanoparticle coatings cuam tshuam rau lawv qhov nqus thiab biodistribution hauv lub cev thiab tseem muaj txiaj ntsig zoo hauv autophagy ntawm nanoparticles [14, 108, 117]. Zoo li feem ntau nanoparticles, IONPs muaj cov hlau oxide core thiab txheej tiv thaiv. Cov txheej txheej saum npoo tuaj yeem txhim kho IONPs muaj nuj nqi thiab lawv cov khoom cytotoxicity. Yog li ntawd, cov txheej txheej saum npoo zoo li qhov tseem ceeb rau kev ua kom zoo ntawm IONPs nrog rau kev ruaj ntseg, biocompatibility, multi-functionalization, zoo biodegradation, hydrophilic interactions, thiab solubility [109]. Cov txheej txheej saum npoo tuaj yeem cuam tshuam nrog IONPs physicochemical cov yam ntxwv suav nrog kev cuam tshuam nrog cov khoom siv lom neeg, cov cellular uptake, hauv vivo txoj hmoo, thiab toxicity. Nws tseem cuam tshuam rau txoj hmoo thiab kev lom neeg ntawm IONPs. Cov txheej txheej muab cov txheej txheem txuas mus rau cov sib txawv molecular ligands xws li tshuaj pawg (piv txwv li, carboxyl thiab hydroxyl) thiab biomolecules (xws li peptides thiab polysaccharides), uas yog hu ua functionalization [6]. Vim yog colloidal instability ntawm liab qab IONPs, ntau lub ntuj thiab hluavtaws txheej txheej xws li chitosan, dextran, citrate, Pluronic, polyethylene glycol (PEG), poly (ethylene) (PEI), polyvinyl cawv (PVA), silica, thiab kub tau raug. siv. PEG yog cov txheej txheem nrov tshaj plaws vim tias nws tiv thaiv kev sib sau ua ke thiab opsonization ntawm nanoparticles. PEI yog siv los xa cov DNA/siRNA.Nyob rau hauv peb cov kev tshawb fawb, peb tau siv dextran, hydrophobic natural polymeric carbohydrate nrog tus nqi nruab nrab [115, 130-134]. Txawm hais tias cov txheej txheem tsim nyog tuaj yeem ua kom ruaj khov IONPs, zam kev sib sau ua ke, thiab tiv thaiv kev sib cais thiab tso tawm cov tshuaj lom ions, muaj cov lus ceeb toom hais txog qhov txheeb ze ntawm cov IONPs ntog. Hauv qhov no, Kazemipour et al. qhia tias 100 mg / kg ntawm IONPs coated los ntawm dextran induced ib tug tseem ceeb txo nyob rau hauv lub siab GSH qib thiab CAT kev ua thiab ib tug tseem ceeb nce nyob rau hauv lub siab MDA theem ntawm nas [135]. Hauv kev kawm Feng, thiab al. tau pom tias PEI-coated IONPs ua rau muaj cytotoxicity hnyav los ntawm ntau lub tshuab xws li ROS ntau lawm thiab apoptosis. Txawm li cas los xij, PEGylated IONPs tau pom cov nyhuv cytotoxic me ntsis tsuas yog nyob rau hauv siab. Tsis tas li ntawd, PEI-coated IONPs nthuav tawm koob tshuaj tiv thaiv kab mob ua rau tuag taus hauv BALB / c nas [136]. Cov txiaj ntsig ntawm kev tshawb fawb hauv vitro tau pom tias cov hlau nplaum nanoparticles coated nrog luv tshaj 0.75 kDa polyethylene oxide (PEO) tails ua rau cytotoxicity thiab muaj kev sib cuam tshuam ntawm PEO tail block ntev nrog toxicity [137]. Badman thiab et al. soj ntsuam cov koob tshuaj-dependent neurotoxicity ntawm dextran-coated IONPs ntawm kab lis kev cai thawj neurons thiab pom tias qhov concentration siab tshaj 20 ug / ml nce cellular ROS thiab ua rau cell tuag [138]. Yog li ntawd lub xub ntiag ntawm cov hlau chelator muaj zog tuaj yeem txhim kho cov txiaj ntsig zoo ntawm IONPs nrog cov txheej txheem sib txawv thiab tiv thaiv lawv cov toxicity ntawm lawv.

Kab lus no yog muab rho tawm los ntawm Bardestani li al. J Nanobiotechnol (2021) 19:327 https://doi.org/10.1186/s12951-021-01059-0