Abstract: Ceria nanoparticles (CeO₂ NPs) have become popular materials in biomedical and industrial fields due to their potential applications in anti-oxidation, cancer therapy, photocatalytic degradation of pollutants, sensors, etc. Many methods, including gas phase, solid phase, liquid phase, and the newly proposed green synthesis method, have been reported for the synthesis of CeO₂ NPs. Due to the wide application of CeO₂ NPs, concerns about their adverse impacts on human health have been raised. This review covers recent studies on the biomedical applications of CeO₂ NPs, including their use in the treatment of various diseases (e.‍g., Alzheimer’s disease, ischemic stroke, retinal damage, chronic inflammation, and cancer). CeO₂ NP toxicity is discussed in terms of the different systems of the human body (e.‍g., cytotoxicity, genotoxicity, respiratory toxicity, neurotoxicity, and hepatotoxicity). This comprehensive review covers both fundamental discoveries and exploratory progress in CeO₂ NP research that may lead to practical developments in the future.

二氧化铈纳米颗粒：生物医学应用和毒性

[1]AbeH, MizoguchiH, EguchiR, et al., 2023. Exploration of heterogeneous catalyst for molecular hydrogen ortho-para conversion. Exploration, 20230040.

[2]AgiA, JuninR, ArsadA, et al., 2019. Synergy of the flow behaviour and disperse phase of cellulose nanoparticles in enhancing oil recovery at reservoir condition. PLoS ONE, 14(9):e0220778.

[3]AliliL, SackM, von MontfortC, et al., 2013. Downregulation of tumor growth and invasion by redox-active nanoparticles. Antioxid Redox Signal, 19(8):765-778.

[4]AndersenMHG, FrederiksenM, SaberAT, et al., 2019. Health effects of exposure to diesel exhaust in diesel-powered trains. Part Fibre Toxicol, 16:21.

[5]ArumugamA, KarthikeyanC, Haja HameedAS, et al., 2015. Synthesis of cerium oxide nanoparticles using Gloriosa superba L. leaf extract and their structural, optical and antibacterial properties. Mater Sci Eng C, 49:408-415.

[6]AsgharzadehF, HashemzadehA, RahmaniF, et al., 2021. Cerium oxide nanoparticles acts as a novel therapeutic agent for ulcerative colitis through anti-oxidative mechanism. Life Sci, 278:119500.

[7]BadiaA, DuarriA, SalasA, et al., 2023. Repeated topical administration of 3 nm cerium oxide nanoparticles reverts disease atrophic phenotype and arrests neovascular degeneration in AMD mouse models. ACS Nano, 17(2):‍910-926.

[8]BalajiS, MandalBK, Vinod Kumar ReddyL, et al., 2020. Biogenic ceria nanoparticles (CeO₂ NPs) for effective photocatalytic and cytotoxic activity. Bioengineering, 7(1):26.

[9]BassousNJ, GarciaCB, WebsterTJ, 2021. A study of the chemistries, growth mechanisms, and antibacterial properties of cerium- and yttrium-containing nanoparticles. ACS Biomater Sci Eng, 7(5):1787-1807.

[10]BhagatS, Srikanth VallabaniNV, ShutthanandanV, et al., 2018. Gold core/ceria shell-based redox active nanozyme mimicking the biological multienzyme complex phenomenon. J Colloid Interface Sci, 513:831-842.

[11]BhattiMT, 2006. Retinitis pigmentosa, pigmentary retinopathies, and neurologic diseases. Curr Neurol Neurosci Rep, 6(5):403-413.

[12]BiswasS, DodwadkarNS, DeshpandePP, et al., 2012. Liposomes loaded with paclitaxel and modified with novel triphenylphosphonium-PEG-PE conjugate possess low toxicity, target mitochondria and demonstrate enhanced antitumor effects in vitro and in vivo. J Control Release, 159(3):393-402.

[13]CafunJD, KvashninaKO, CasalsE, et al., 2013. Absence of Ce³⁺ sites in chemically active colloidal ceria nanoparticles. ACS Nano, 7(12):10726-10732.

[14]CasalsE, ZengML, Parra-RobertM, et al., 2020. Cerium oxide nanoparticles: advances in biodistribution, toxicity, and preclinical exploration. Small, 16(20):1907322.

[15]CelardoI, PedersenJZ, TraversaE, et al., 2011. Pharmacological potential of cerium oxide nanoparticles. Nanoscale, 3(4):1411-1420.

[16]CharbgooF, RamezaniM, DarroudiM, 2017. Bio-sensing applications of cerium oxide nanoparticles: advantages and disadvantages. Biosens Bioelectron, 96:33-43.

[17]ChatzimentorI, TsamesidisI, IoannouME, et al., 2023. Study of biological behavior and antimicrobial properties of cerium oxide nanoparticles. Pharmaceutics, 15(10):2509.

[18]ChaudhuryK, BabuKN, SinghAK, et al., 2013. Mitigation of endometriosis using regenerative cerium oxide nanoparticles. Nanomedicine, 9(3):439-448.

[19]ChenBH, Stephen InbarajB, 2018. Various physicochemical and surface properties controlling the bioactivity of cerium oxide nanoparticles. Crit Rev Biotechnol, 38(7):1003-1024.

[20]ChenHQ, ZhaoRF, WangB, et al., 2018. Acute oral administration of single-walled carbon nanotubes increases intestinal permeability and inflammatory responses: association with the changes in gut microbiota in mice. Adv Healthc Mater, 7(13):1701313.

[21]ChengGL, GuoW, HanL, et al., 2013. Cerium oxide nanoparticles induce cytotoxicity in human hepatoma SMMC-7721 cells via oxidative stress and the activation of MAPK signaling pathways. Toxicol in Vitro, 27(3):1082-1088.

[22]ChoiJH, LeeH, LeeH, et al., 2021. Dopant-dependent toxicity of CeO₂ nanoparticles is associated with dynamic changes in H3K4me3 and H3K27me3 and transcriptional activation of NRF2 gene in HaCaT human keratinocytes. Int J Mol Sci, 22(6):3087.

[23]ChoiSW, ChaBG, KimJ, 2020. Therapeutic contact lens for scavenging excessive reactive oxygen species on the ocular surface. ACS Nano, 14(2):2483-2496.

[24]CocchiV, GasperiniS, HreliaP, et al., 2020. Novel psychoactive phenethylamines: impact on genetic material. Int J Mol Sci, 21(24):9616.

[25]ConesaJ, 1995. Computer modeling of surfaces and defects on cerium dioxide. Surf Sci, 339(3):337-352.

[26]CormaA, AtienzarP, GarcíaH, et al., 2004. Hierarchically mesostructured doped CeO₂ with potential for solar-cell use. Nat Mater, 3(6):394-397.

[27]CuiW, WangY, LuoC, et al., 2022. Nanoceria for ocular diseases: recent advances and future prospects. Materi Today Nano, 18:100218.

[28]DarroudiM, SaraniM, Kazemi OskueeR, et al., 2014a. Green synthesis and evaluation of metabolic activity of starch mediated nanoceria. Ceram Int, 40(1):2041-2045.

[29]DarroudiM, HoseiniSJ, Kazemi OskueeR, et al., 2014b. Food-directed synthesis of cerium oxide nanoparticles and their neurotoxicity effects. Ceram Int, 40(5):‍7425-7430.

[30]DasM, PatilS, BhargavaN, et al., 2007. Auto-catalytic ceria nanoparticles offer neuroprotection to adult rat spinal cord neurons. Biomaterials, 28(10):1918-1925.

[31]DasS, DowdingJM, KlumpKE, et al., 2013. Cerium oxide nanoparticles: applications and prospects in nanomedicine. Nanomedicine (Lond), 8(9):1483-1508.

[32]DiabatéS, ArmandL, MurugadossS, et al., 2020. Air–liquid interface exposure of lung epithelial cells to low doses of nanoparticles to assess pulmonary adverse effects. Nanomaterials, 11(1):65.

[33]DowdingJM, DasS, KumarA, et al., 2013. Cellular interaction and toxicity depend on physicochemical properties and surface modification of redox-active nanomaterials. ACS Nano, 7(6):4855-4868.

[34]DuanHH, WangDS, LiYD, 2015. Green chemistry for nanoparticle synthesis. Chem Soc Rev, 44(16):5778-5792.

[35]DuanY, LiangL, YeFG, et al., 2023. A Ce-MOF@polydopamine composite nanozyme as an efficient scavenger for reactive oxygen species and iron in thalassemia disease therapy. Nanoscale, 15(33):13574-13582.

[36]ElahiB, MirzaeeM, DarroudiM, et al., 2019. Preparation of cerium oxide nanoparticles in Salvia macrosiphon Boiss seeds extract and investigation of their photo-catalytic activities. Ceram Int, 45(4):4790-4797.

[37]EstevezAY, PritchardS, HarperK, et al., 2011. Neuroprotective mechanisms of cerium oxide nanoparticles in a mouse hippocampal brain slice model of ischemia. Free Radic Biol Med, 51(6):1155-1163.

[38]FabianoB, ReverberiAP, VarbanovPS, 2019. Safety opportunities for the synthesis of metal nanoparticles and short-cut approach to workplace risk evaluation. J Clean Prod, 209:297-308.

[39]FengKJ, YangYH, WangZJ, et al., 2006. A nano-porous CeO₂/Chitosan composite film as the immobilization matrix for colorectal cancer DNA sequence-selective electrochemical biosensor. Talanta, 70(3):561-565.

[40]FioraniL, PassacantandoM, SantucciS, et al., 2015. Cerium oxide nanoparticles reduce microglial activation and neurodegenerative events in light damaged retina. PLoS ONE, 10(10):e0140387.

[41]FiordelisiA, PiscitelliP, TrimarcoB, et al., 2017. The mechanisms of air pollution and particulate matter in cardiovascular diseases. Heart Fail Rev, 22(3):337-347.

[42]FisherTJ, ZhouYY, WuTS, et al., 2019. Structure‍–‍activity relationship of nanostructured ceria for the catalytic generation of hydroxyl radicals. Nanoscale, 11(10):‍4552-4561.

[43]GenchiG, SinicropiMS, LauriaG, et al., 2020. The effects of cadmium toxicity. Int J Environ Res Public Health, 17(11):3782.

[44]GenchiGG, Degl'InnocentiA, SalgarellaAR, et al., 2018. Modulation of gene expression in rat muscle cells following treatment with nanoceria in different gravity regimes. Nanomedicine (Lond), 13(22):2821-2833.

[45]GenchiGG, Degl'InnocentiA, MartinelliC, et al., 2021. Cerium oxide nanoparticle administration to skeletal muscle cells under different gravity and radiation conditions. ACS Appl Mater Interfaces, 13(34):40200-40213.

[46]GieseB, KlaessigF, ParkB, et al., 2018. Risks, release and concentrations of engineered nanomaterial in the environment. Sci Rep, 8:1565.

[47]GligaAR, EdoffK, CaputoF, et al., 2017. Cerium oxide nanoparticles inhibit differentiation of neural stem cells. Sci Rep, 7:9284.

[48]GopinathK, KarthikaV, SundaravadivelanC, et al., 2015. Mycogenesis of cerium oxide nanoparticles using Aspergillus niger culture filtrate and their applications for antibacterial and larvicidal activities. J Nanostruct Chem, 5(3):295-303.

[49]GosensI, MathijssenLEAM, BokkersBGH, et al., 2014. Comparative hazard identification of nano- and micro-sized cerium oxide particles based on 28-day inhalation studies in rats. Nanotoxicology, 8(6):643-653.

[50]GuoLM, LiZ, MarcusK, et al., 2017. Periodically patterned Au-TiO₂ heterostructures for photoelectrochemical sensor. ACS Sens, 2(5):621-625.

[51]HardasSS, ButterfieldDA, SultanaR, et al., 2010. Brain distribution and toxicological evaluation of a systemically delivered engineered nanoscale ceria. Toxicol Sci, 116(2):562-576.

[52]HasanzadehL, Kazemi OskueeR, SadriK, et al., 2018. Green synthesis of labeled CeO₂ nanoparticles with ^99mTc and its biodistribution evaluation in mice. Life Sci, 212:233-240.

[53]HassanpourM, Salavati-NiasariM, Safardoust-HojaghanH, 2021. Sol-gel synthesis and characterization of Co₃O₄/CeO₂ nanocomposites and its application for photocatalytic discoloration of organic dye from aqueous solutions. Environ Sci Pollut Res, 28(6):7001-7015.

[54]HeLZ, HuangGN, LiuHX, et al., 2020. Highly bioactive zeolitic imidazolate framework-8-capped nanotherapeutics for efficient reversal of reperfusion-induced injury in ischemic stroke. Sci Adv, 6(12):eaay9751.

[55]HeckertEG, SealS, SelfWT, 2008. Fenton-like reaction catalyzed by the rare earth inner transition metal cerium. Environ Sci Technol, 42(13):5014-5019.

[56]HegazyMA, MakladHM, SamyDM, et al., 2017. Cerium oxide nanoparticles could ameliorate behavioral and neurochemical impairments in 6-hydroxydopamine induced Parkinson’s disease in rats. Neurochem Int, 108:361-371.

[57]HirstSM, KarakotiAS, TylerRD, et al., 2009. Anti-inflammatory properties of cerium oxide nanoparticles. Small, 5(24):2848-2856.

[58]HirstSM, KarakotiA, SinghS, et al., 2013. Bio-distribution and in vivo antioxidant effects of cerium oxide nanoparticles in mice. Environ Toxicol, 28(2):107-118.

[59]HuFX, ChenSH, WangCY, et al., 2012. Multi-wall carbon nanotube-polyaniline biosensor based on lectin-carbohydrate affinity for ultrasensitive detection of Con A. Biosens Bioelectron, 34(1):202-207.

[60]JiHI, DavenportTC, GopalCB, et al., 2016. Extreme high temperature redox kinetics in ceria: exploration of the transition from gas-phase to material-kinetic limitations. Phys Chem Chem Phys, 18(31):21554-21561.

[61]JoorablooA, LiuTQ, 2024. Recent advances in reactive oxygen species scavenging nanomaterials for wound healing. Exploration, 20230066.

[62]KalashnikovaI, ChungSJ, NafiujjamanM, et al., 2020. Ceria-based nanotheranostic agent for rheumatoid arthritis. Theranostics, 10(26):11863-11880.

[63]KannanSK, SundrarajanM, 2014. A green approach for the synthesis of a cerium oxide nanoparticle: characterization and antibacterial activity. Int J Nanosci, 13(3):1450018.

[64]KargarH, GhazaviH, DarroudiM, 2015. Size-controlled and bio-directed synthesis of ceria nanopowders and their in vitro cytotoxicity effects. Ceram Int, 41(3):4123-4128.

[65]KarimiA, OthmanA, AndreescuS, 2016. Portable enzyme-paper biosensors based on redox-active CeO₂ nanoparticles. Methods Enzymol, 571:177-195.

[66]KhanF, LeeJW, PhamDNT, et al., 2020. Antibiofilm action of ZnO, SnO₂ and CeO₂ nanoparticles towards grampositive biofilm forming pathogenic bacteria. Recent Pat Nanotechnol, 14(3):239-249.

[67]KhanSA, AhmadA, 2013. Fungus mediated synthesis of biomedically important cerium oxide nanoparticles. Mater Res Bull, 48(10):4134-4138.

[68]KhatamiM, SaraniM, MosazadehF, et al., 2019. Nickel-doped cerium oxide nanoparticles: green synthesis using stevia and protective effect against harmful ultraviolet rays. Molecules, 24(24):4424.

[69]KiefferJ, SinghS, DhillonBS, et al., 2020. Ceria nanoparticles mitigate the iron oxidative toxicity of human retinal pigment epithelium. Cureus, 12(8):e9675.

[70]KimCK, KimT, ChoiIY, et al., 2012. Ceria nanoparticles that can protect against ischemic stroke. Angew Chem Int Ed, 51(44):11039-11043.

[71]KimM, ParkG, LeeH, 2021. Local structure and redox properties of amorphous CeO₂-TiO₂ prepared using the H₂O₂-modified sol-gel method. Nanomaterials, 11(8):2148.

[72]KitchinKT, StirdivantS, RobinetteBL, et al., 2017. Metabolomic effects of CeO₂, SiO₂ and CuO metal oxide nanomaterials on HepG2 cells. Part Fibre Toxicol, 14:50.

[73]KolliMB, ManneNDPK, ParaR, et al., 2014. Cerium oxide nanoparticlesattenuate monocrotaline induced right ventricular hypertrophy following pulmonary arterial hypertension. Biomaterials, 35(37):9951-9962.

[74]KongT, ZhangSH, ZhangC, et al., 2020. The effects of 50 nm unmodified nano-ZnO on lipid metabolism and semen quality in male mice. Biol Trace Elem Res, 194(2):432-442.

[75]KooS, SohnHS, KimTH, et al., 2023. Ceria-vesicle nanohybrid therapeutic for modulation of innate and adaptive immunity in a collagen-induced arthritis model. Nat Nanotechnol, 18(12):1502-1514.

[76]KorscheltK, SchwidetzkyR, PfitznerF, et al., 2018. CeO_2-x nanorods with intrinsic urease-like activity. Nanoscale, 10(27):13074-13082.

[77]KuznetsovD, DezhurovS, KrylskyD, et al., 2022. Use of folic acid nanosensors with excellent photostability for hybrid imaging. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(9):784-790.

[78]LandsiedelR, Ma-HockL, HofmannT, et al., 2014. Application of short-term inhalation studies to assess the inhalation toxicity of nanomaterials. Part Fibre Toxicol, 11:16.

[79]LariaA, LuratiAM, MarrazzaM, et al., 2016. The macrophages in rheumatic diseases. J Inflamm Res, 9:1-11.

[80]LiHL, WuCY, LiY, et al., 2012. Role of flue gas components in mercury oxidation over TiO2 supported MnOx-CeO2 mixed-oxide at low temperature. J Hazard Mater, 243:117-123.

[81]LiX, HanZH, WangTY, et al., 2022. Cerium oxide nanoparticles with antioxidative neurorestoration for ischemic stroke. Biomaterials, 291:121904.

[82]LiY, LiP, YuH, et al., 2016. Recent advances (2010‍–‍2015) in studies of cerium oxide nanoparticles’ health effects. Environ Toxicol Pharmacol, 44:25-29.

[83]LiYB, ZengSJ, HaoJH, 2019. Non-invasive optical guided tumor metastasis/vessel imaging by using lanthanide nanoprobe with enhanced down-shifting emission beyond 1500 nm. ACS Nano, 13(1):248-259.

[84]LiYH, LiuJH, FuCC, et al., 2022. CeO₂ nanoparticles modulate Cu‍–‍Zn superoxide dismutase and lipoxygenase-IV isozyme activities to alleviate membrane oxidative damage to improve rapeseed salt tolerance. Environ Sci Nano, 9(3):1116-1132.

[85]LinSJ, WangX, JiZX, et al., 2014. Aspect ratio plays a role in the hazard potential of CeO₂ nanoparticles in mouse lung and zebrafish gastrointestinal tract. ACS Nano, 8(5):4450-4464.

[86]LinWS, HuangYW, ZhouXD, et al., 2006. Toxicity of cerium oxide nanoparticles in human lung cancer cells. Int J Toxicol, 25(6):451-457.

[87]LiuD, LuG, ShiB, et al., 2023. ROS-scavenging hydrogels synergize with neural stem cells to enhance spinal cord injury repair via regulating microenvironment and facilitating nerve regeneration. Adv Healthc Mater, 12:2300123.

[88]LiuJJ, ChenYL, WangWF, et al., 2016. “Switch-on” fluorescent sensing of ascorbic acid in food samples based on carbon quantum dots–MnO₂ probe. J Agric Food Chem, 64(1):371-380.

[89]LiuXN, LuQF, WeiMZ, et al., 2015. Facile electrospinning of CeO₂/Bi₂WO₆ heterostructured nanofibers with excellent visible-light-driven photocatalytic performance. Chem-Asian J, 10(8):1710-1716.

[90]LiuXY, ChenZX, BaiJY, et al., 2023. Multifunctional hydrogel eye drops for synergistic treatment of ocular inflammatory disease. ACS Nano, 17(24):25377-25390.

[91]LuHB, WanL, LiXL, et al., 2022. Combined synthesis of cerium oxide particles for effective anti-bacterial and anti-cancer nanotherapeutics. Int J Nanomedicine, 17:5733-5746.

[92]LuJQ, LiuJY, LiA, 2022. Roles of neutrophil reactive oxygen species (ROS) generation in organ function impairment in sepsis. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(6):437-450.

[93]MaYY, LiP, ZhaoLE, et al., 2021. Size-dependent cytotoxicity and reactive oxygen species of cerium oxide nanoparticles in human retinal pigment epithelia cells. Int J Nanomedicine, 16:5333-5341.

[94]MachhiJ, YeapuriP, MarkovicM, et al., 2022. Europium-doped cerium oxide nanoparticles for microglial amyloid beta clearance and homeostasis. ACS Chem Neurosci, 13(8):1232-1244.

[95]MaiHX, SunLD, ZhangYW, et al., 2005. Shape-selective synthesis and oxygen storage behavior of ceria nanopolyhedra, nanorods, and nanocubes. J Phys Chem B, 109(51):24380-24385.

[96]MalleshappaJ, NagabhushanaH, SharmaSC, et al., 2015. Leucas aspera mediated multifunctional CeO₂ nanoparticles: structural, photoluminescent, photocatalytic and antibacterial properties. Spectrochim Acta Part A Mol Biomol Spectrosc, 149:452-462.

[97]MarinoA, Tonda-TuroC, de PasqualeD, et al., 2017. Gelatin/nanoceria nanocomposite fibers as antioxidant scaffolds for neuronal regeneration. Biochim Biophys Acta (BBA)-Gen Subj, 1861(2):386-395.

[98]Martínez-AriasA, Fernández-GarcíaM, BelverC, et al., 2000. EPR study on oxygen handling properties of ceria, zirconia and Zr‍–‍Ce (1:‍1) mixed oxide samples. Catal Lett, 65(4):197-204.

[99]MaskreyBH, MegsonIL, WhitfieldPD, et al., 2011. Mechan

[100]isms of resolution of inflammation: a focus on cardiovascular disease. Arterioscler Thromb Vasc Biol, 31(5):‍1001-1006.

[101]MengTJ, NsabimanaA, ZengT, et al., 2020. Preparation of Pt anchored on cerium oxide and ordered mesoporous carbon tri-component composite for electrocatalytic oxidation of adrenaline. Mater Sci Eng: C, 110:110747.

[102]MittalS, PandeyAK, 2018. Corrigendum to “cerium oxide nanoparticles induced toxicity in human lung cells: role of ROS mediated DNA damage and apoptosis”. Biomed Res Int, 2018:6349540.

[103]Mohammad, KhanUA, WarsiMH, et al., 2023. Intranasal cer

[104]ium oxide nanoparticles improves locomotor activity and reduces oxidative stress and neuroinflammation in haloperidol-induced parkinsonism in rats. Front Pharmacol, 14:1188470.

[105]MollarasouliF, ZorE, OzcelikayG, et al., 2021. Magnetic nanoparticles in developing electrochemical sensors for pharmaceutical and biomedical applications. Talanta, 226:122108.

[106]NadeemM, KhanR, AfridiK, et al., 2020. Green synthesis of cerium oxide nanoparticles (CeO₂ NPs) and their antimicrobial applications: a review. Int J Nanomedicine, 15:5951-5961.

[107]NaidiSN, HarunsaniMH, TanAL, et al., 2021. Green-synthesized CeO₂ nanoparticles for photocatalytic, antimicrobial, antioxidant and cytotoxicity activities. J Mater Chem B, 9(28):5599-5620.

[108]NakamuraS, IshiharaM, SatoY, et al., 2020. Concentrated bioshell calcium oxide (BiSCaO) water kills pathogenic microbes: characterization and activity. Molecules, 25(13):3001.

[109]NalabotuSK, KolliMB, TriestWE, et al., 2011. Intratracheal instillation of cerium oxide nanoparticles induces hepatic toxicity in male Sprague-Dawley rats. Int J Nanomedicine, 6:2327-2335.

[110]NefedovaA, RausaluK, ZusinaiteE, et al., 2022. Antiviral efficacy of cerium oxide nanoparticles. Sci Rep, 12:18746.

[111]NelsonBC, JohnsonME, WalkerML, et al., 2016. Antioxidant cerium oxide nanoparticles in biology and medicine. Antioxidants, 5(2):15.

[112]NemmarA, Al-SalamS, NuamanSA, et al., 2021. Exacerbation of coagulation and cardiac injury in rats with cisplatin-induced nephrotoxicity following intratracheal instillation of cerium oxide nanoparticles. Cell Physiol Biochem, 55(1):1-16.

[113]NiDL, WeiH, ChenWY, et al., 2019. Ceria nanoparticles meet hepatic ischemia-reperfusion injury: the perfect imperfection. Adv Mater, 31(40):1902956.

[114]NiuJL, AzferA, RogersLM, et al., 2007. Cardioprotective effects of cerium oxide nanoparticles in a transgenic murine model of cardiomyopathy. Cardiovasc Res, 73(3):549-559.

[115]NiuJL, WangKK, KolattukudyPE, 2011. Cerium oxide nanoparticles inhibits oxidative stress and nuclear factor-κB activation in H9c2 cardiomyocytes exposed to cigarette smoke extract. J Pharmacol Exp Ther, 338(1):53-61.

[116]NyokaM, ChoonaraYE, KumarP, et al., 2020. Synthesis of cerium oxide nanoparticles using various methods: implications for biomedical applications. Nanomaterials, 10(2):242.

[117]OuyangXL, TangL, FengCY, et al., 2020. Au/CeO₂/g-C₃N₄ heterostructures: designing a self-powered aptasensor for ultrasensitive detection of Microcystin-LR by density functional theory. Biosens Bioelectron, 164:112328.

[118]ParsaeiR, KazemzadehY, RiaziM, 2020. Study of asphaltene precipitation during CO₂ injection into oil reservoirs in the presence of iron oxide nanoparticles by interfacial tension and bond number measurements. ACS Omega, 5(14):7877-7884.

[119]PatilD, DungNQ, JungH, et al., 2012. Enzymatic glucose biosensor based on CeO₂ nanorods synthesized by non-isothermal precipitation. Biosens Bioelectron, 31(1):176-181.

[120]PauluhnJ, 2018. Fate of inhaled nano-CeO₂ revisited: predicting the unpredictable. Regul Toxicol Pharmacol, 97:63-70.

[121]Pemartin-BiernathK, Vela-GonzálezAV, Moreno-TrejoMB, et al., 2016. Synthesis of mixed Cu/Ce oxide nanoparticles by the oil-in-water microemulsion reaction method. Materials, 9(6):480.

[122]PirmohamedT, DowdingJM, SinghS, et al., 2010. Nanoceria exhibit redox state-dependent catalase mimetic activity. Chem Commun, 46(16):2736-2738.

[123]PopovAL, PopovaNR, SeleznevaII, et al., 2016. Cerium oxide nanoparticles stimulate proliferation of primary mouse embryonic fibroblasts in vitro. Mater Sci Eng C, 68:‍406-413.

[124]PrantiAS, LoofD, KunzS, et al., 2019. Ligand-linked nanoparticles-based hydrogen gas sensor with excellent homogeneous temperature field and a comparative stability evaluation of different ligand-linked catalysts. Sensors, 19(5):1205.

[125]PreaubertL, CourbiereB, AchardV, et al., 2016. Cerium dioxide nanoparticles affect in vitro fertilization in mice. Nanotoxicology, 10(1):111-117.

[126]QianXC, QuQ, LiL, et al., 2018. Ultrasensitive electrochemical detection of Clostridium perfringens DNA based morphology-dependent DNA adsorption properties of CeO₂ nanorods in dairy products. Sensors, 18(6):1878.

[127]RaemyDO, LimbachLK, Rothen-RutishauserB, et al., 2011. Cerium oxide nanoparticle uptake kinetics from the gas-phase into lung cells in vitro is transport limited. Eur J Pharm Biopharm, 77(3):368-375.

[128]RajanAR, RajanA, JohnA, et al., 2019. Green synthesis of CeO₂ nanostructures by using Morus nigra fruit extract and its antidiabetic activity. AIP Conf Proc, 2105(1):020008.

[129]RajendranS, KhanMM, GraciaF, et al., 2016. Ce³⁺-ion-induced visible-light photocatalytic degradation and electrochemical activity of ZnO/CeO₂ nanocomposite. Sci Rep, 6:31641.

[130]RenSS, ZhouY, ZhengK, et al., 2022. Cerium oxide nanoparticles loaded nanofibrous membranes promote bone regeneration for periodontal tissue engineering. Bioact Mater, 7:242-253.

[131]RobbMA, McInnesPM, CaliffRM, 2016. Biomarkers and surrogate endpoints: developing common terminology and definitions. JAMA, 315(11):1107-1108.

[132]Rodea-PalomaresI, GonzaloS, Santiago-MoralesJ, et al., 2012. An insight into the mechanisms of nanoceria toxicity in aquatic photosynthetic organisms. Aquat Toxicol, 122-123:133-143.

[133]RosárioF, CostaC, LopesCB, et al., 2022. In vitro hepatotoxic and neurotoxic effects of titanium and cerium dioxide nanoparticles, arsenic and mercury co-exposure. Int J Mol Sci, 23(5):2737.

[134]RzigalinskiBA, MeehanK, DavisRM, et al., 2006. Radical nanomedicine. Nanomedicine (Lond), 1(4):399-412.

[135]RzigalinskiBA, SealS, BaileyD, et al., 2009. Cerium Oxide Nanoparticles and Use in Enhancing Cell Survivability. US Patent 7534453.

[136]SackM, AliliL, KaramanE, et al., 2014. Combination of conventional chemotherapeutics with redox-active cerium oxide nanoparticles—a novel aspect in cancer therapy. Mol Cancer Ther, 13(7):1740-1749.

[137]SakthirajK, KarthikeyanB, 2020. Synthesis and characterization of cerium oxide nanoparticles using different solvents for electrochemical applications. Appl Phys A, 126:52.

[138]SangsefidiFS, NejatiM, VerdiJ, et al., 2017. Green synthesis and characterization of cerium oxide nanostructures in the presence carbohydrate sugars as a capping agent and investigation of their cytotoxicity on the mesenchymal stem cell. J Cleaner Prod, 156:741-749.

[139]SarnatskayaV, ShlapaY, YushkoL, et al., 2020. Biological activity of cerium dioxide nanoparticles. J Biomed Mater Res Part A, 108(8):1703-1712.

[140]SauerUG, VogelS, AumannA, et al., 2014. Applicability of rat precision-cut lung slices in evaluating nanomaterial cytotoxicity, apoptosis, oxidative stress, and inflammation. Toxicol Appl Pharmacol, 276(1):1-20.

[141]SayleDC, MaicaneanuSA, WatsonGW, 2002. Atomistic models for CeO2(111), (110), and (100) nanoparticles, supported on yttrium-stabilized zirconia. J Am Chem Soc, 124(38):11429-11439.

[142]SayleTXT, ParkerSC, SayleDC, 2004. Shape of CeO₂ nanoparticles using simulated amorphisation and recrystallisation. Chem Commun, (21):2438-2439.

[143]SchreiberA, MarxJ, ZappP, 2021. Life Cycle Assessment studies of rare earths production – findings from a systematic review. Sci Total Environ, 791:148257.

[144]SchubertD, DarguschR, RaitanoJ, et al., 2006. Cerium and yttrium oxide nanoparticles are neuroprotective. Biochem Biophys Res Commun, 342(1):86-91.

[145]SchwotzerD, ErnstH, SchaudienD, et al., 2017. Effects from a 90-day inhalation toxicity study with cerium oxide and barium sulfate nanoparticles in rats. Part Fibre Toxicol, 14:23.

[146]ScutieroG, IannoneP, BernardiG, et al., 2017. Oxidative stress and endometriosis: a systematic review of the literature. Oxid Med Cell Longev, 2017:7265238.

[147]SelvarajV, ManneNDPK, ArvapalliR, et al., 2015. Effect of cerium oxide nanoparticles on sepsis induced mortality and NF-‍κB signaling in cultured macrophages. Nanomedicine (Lond), 10(8):1275-1288.

[148]SepanjniaA, GhasemiH, MohseniR, et al., 2020. Effect of cerium oxide nanoparticles on oxidative stress biomarkers in rats’ kidney, lung, and serum. Iran Biomed J, 24(4):251-256.

[149]SethiP, JyotiA, SinghR, et al., 2008. Aluminium-induced electrophysiological, biochemical and cognitive modifications in the hippocampus of aging rats. NeuroToxicology, 29(6):1069-1079.

[150]ShcherbakovAB, ReukovVV, YakimanskyAV, et al., 2021. CeO₂ nanoparticle-containing polymers for biomedical applications: a review. Polymers, 13(6):924.

[151]ShehataN, KandasI, SamirE, 2020. In-situ gold-ceria nanoparticles: superior optical fluorescence quenching sensor for dissolved oxygen. Nanomaterials, 10(2):314.

[152]ShenGL, LiuM, WangZ, et al., 2018. Hierarchical structure and catalytic activity of flower-like CeO₂ spheres prepared via a hydrothermal method. Nanomaterials, 8(10):773.

[153]SinghA, HussainI, SinghNB, et al., 2019. Uptake, translocation and impact of green synthesized nanoceria on growth and antioxidant enzymes activity of Solanum lycopersicum L. Ecotoxicol Environ Saf, 182:109410.

[154]SinghKRB, NayakV, SarkarT, et al., 2020. Cerium oxide nanoparticles: properties, biosynthesis and biomedical application. RSC Adv, 10(45):27194-27214.

[155]SinghS, DosaniT, KarakotiAS, et al., 2011. A phosphate-dependent shift in redox state of cerium oxide nanoparticles and its effects on catalytic properties. Biomaterials, 32(28):6745-6753.

[156]SudhakarV, RichardsonRM, 2019. Gene therapy for neurodegenerative diseases. Neurotherapeutics, 16(1):166-175.

[157]SunY, SunXL, LiX, et al., 2021. A versatile nanocomposite based on nanoceria for antibacterial enhancement and protection from aPDT-aggravated inflammation via modu

[158]lation of macrophage polarization. Biomaterials, 268:120614.

[159]SunYH, ZhaoCQ, GaoN, et al., 2017. Stereoselective nanozyme based on ceria nanoparticles engineered with amino acids. Chem-A Eur J, 23(72):18146-18150.

[160]TakahashiT, MarushimaA, NagasakiY, et al., 2020. Novel neuroprotection using antioxidant nanoparticles in a mouse model of head trauma. J Trauma Acute Care Surg, 88(5):677-685.

[161]TarafdarA, PulaG, 2018. The role of NADPH oxidases and oxidative stress in neurodegenerative disorders. Int J Mol Sci, 19(12):3824.

[162]TarnuzzerRW, ColonJ, PatilS, et al., 2005. Vacancy engin

[163]eered ceria nanostructures for protection from radiation-induced cellular damage. Nano Lett, 5(12):2573-2577.

[164]TentschertJ, LauxP, JungnickelH, et al., 2020. Organ burden of inhaled nanoceria in a 2-year low-dose exposure study: dump or depot? Nanotoxicology, 14(4):554-576.

[165]ThillA, ZeyonsO, SpallaO, et al., 2006. Cytotoxicity of CeO₂ nanoparticles for Escherichia coli. Physico-chemical insight of the cytotoxicity mechanism. Environ Sci Technol, 40(19):6151-6156.

[166]TisiA, FlatiV, Delle MonacheS, et al., 2020. Nanoceria particles are an eligible candidate to prevent age-related macu

[167]lar degeneration by inhibiting retinal pigment epithelium cell death and autophagy alterations. Cells, 9(7):1617.

[168]TisiA, PulciniF, CarozzaG, et al., 2022. Antioxidant properties of cerium oxide nanoparticles prevent retinal neovascular alterations in vitro and in vivo. Antioxidants, 11(6):1133.

[169]TsunekawaS, IshikawaK, LiZQ, et al., 2000. Origin of anomalous lattice expansion in oxide nanoparticles. Phys Rev Lett, 85(16):3440-3443.

[170]TurrensJF, 2003. Mitochondrial formation of reactive oxygen species. J Physiol, 552(Pt 2):335-344.

[171]TürkezH, ArslanME, SönmezE, et al., 2017. Toxicogenomic responses of human alveolar epithelial cells to tungsten boride nanoparticles. Chem-Biol Interact, 273:257-265.

[172]van DamL, DansenTB, 2020. Cross-talk between redox signalling and protein aggregation. Biochem Soc Trans, 48(2):379-397.

[173]VenkateshKS, GopinathK, PalaniNS, et al., 2016. Plant pathogenic fungus F. solani mediated biosynthesis of nanoceria: antibacterial and antibiofilm activity. RSC Adv, 6(48):42720-42729.

[174]VerstraelenS, RemyS, CasalsE, et al., 2014. Gene expression profiles reveal distinct immunological responses of cobalt and cerium dioxide nanoparticles in two in vitro lung epithelial cell models. Toxicol Lett, 228(3):157-169.

[175]VillaS, MaggioniD, HamzaH, et al., 2020. Natural molecule coatings modify the fate of cerium dioxide nanoparticles in water and their ecotoxicity to Daphnia magna. Environ Pollut, 257:113597.

[176]VlachouE, MargaritiA, PapaefstathiouGS, et al., 2020. Voltammetric determination of Pb(II) by a Ca-MOF-modified carbon paste electrode integrated in a 3D-printed device. Sensors, 20(16):4442.

[177]WahlgrenNG, AhmedN, 2004. Neuroprotection in cerebral ischaemia: facts and fancies – the need for new approaches. Cerebrovasc Dis, 17(Suppl 1):153-166.

[178]WangSG, LawsonR, RayPC, et al., 2011. Toxic effects of gold nanoparticles on Salmonella typhimurium bacteria. Toxicol Ind Health, 27(6):547-554.

[179]WengQJ, SunH, FangCY, et al., 2021. Catalytic activity tunable ceria nanoparticles prevent chemotherapy-induced acute kidney injury without interference with chemotherapeutics. Nat Commun, 12:1436.

[180]WitikaBA, MakoniPA, MweetwaLL, et al., 2020. Nano-biomimetic drug delivery vehicles: potential approaches for COVID-19 treatment. Molecules, 25(24):5952.

[181]WongLL, HirstSM, PyeQN, et al., 2013. Catalytic nanoceria are preferentially retained in the rat retina and are not cytotoxic after intravitreal injection. PLoS ONE, 8(3):e58431.

[182]WongLL, PyeQN, ChenLJ, et al., 2015. Defining the catalytic activity of nanoceria in the P23H-1 rat, a photoreceptor degeneration model. PLoS ONE, 10(3):e0121977.

[183]WuHF, ZhangXY, LiaoPQ, et al., 2005. NMR spectroscopic-based metabonomic investigation on the acute biochemical effects induced by Ce(NO₃)₃ in rats. J Inorg Biochem, 99(11):2151-2160.

[184]WuLY, LiuGY, WangWY, et al., 2020. Cyclodextrin-modified CeO₂ nanoparticles as a multifunctional nanozyme for combinational therapy of psoriasis. Int J Nanomedicine, 15:2515-2527.

[185]XiuMH, LiZZ, ChenDC, et al., 2020. Interrelationships between BDNF, superoxide dismutase, and cognitive impairment in drug-naive first-episode patients with schizophrenia. Schizophr Bull, 46(6):1498-1510.

[186]XuHT, LiSQ, MaXX, et al., 2023. Cerium oxide nanoparticles in diabetic foot ulcer management: advances, limitations, and future directions. Colloids Surf B Biointerfaces, 231:113535.

[187]YangBW, ChenY, ShiJL, 2019a. Nanocatalytic medicine. Adv Mater, 31(39):1901778.

[188]YangBW, ChenY, ShiJL, 2019b. Reactive oxygen species (ROS)‍-based nanomedicine. Chem Rev, 119(8):4881-4985.

[189]YangQ, WuXQ, PengHL, et al., 2018a. Simultaneous phase-inversion and imprinting based sensor for highly sensitive and selective detection of bisphenol A. Talanta, 176:595-603.

[190]YangQ, LiJH, WangXY, et al., 2018b. Strategies of molecular imprinting-based fluorescence sensors for chemical and biological analysis. Biosen Bioelectron, 112:54-71.

[191]YangSM, KimSRN, YounWK, et al., 2015. Generation of charged nanoparticles during thermal evaporation of silver at atmospheric pressure. J Nanosci Nanotechnol, 15(11):8418-8423.

[192]YaoW, YaoJL, QianFF, et al., 2021. Paclitaxel-loaded and folic acid-modified PLGA nanomedicine with glutathione response for the treatment of lung cancer. Acta Biochim Biophys Sin, 53(8):1027-1036.

[193]YeungCMY, YuKMK, FuQJ, et al., 2005. Engineering Pt in ceria for a maximum metal‍–‍support interaction in catalysis. J Am Chem Soc, 127(51):18010-18011.

[194]YiZG, LuoZC, QinX, et al., 2020. Lanthanide-activated nanoparticles: a toolbox for bioimaging, therapeutics, and neuromodulation. Acc Chem Res, 53(11):2692-2704.

[195]YinLX, WangYQ, PangGS, et al., 2002. Sonochemical synthesis of cerium oxide nanoparticles-effect of additives and quantum size effect. J Colloid Interface Sci, 246(1):78-84.

[196]YouCG, ZhuZK, WangSS, et al., 2023. Nanosilver alleviates foreign body reaction and facilitates wound repair by regulating macrophage polarization. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 24(6):510-523.

[197]YouGX, HouJ, XuY, et al., 2020. Surface properties and environmental transformations controlling the bioaccumulation and toxicity of cerium oxide nanoparticles: a critical review. In: de Voogt P (Ed.), Reviews of Environmental Contamination and Toxicology Volume 253. Springer, Cham, p.155-206.

[198]YulizarY, JuliyantoS, Sudirman, et al., 2021. Novel sol-gel synthesis of CeO₂ nanoparticles using Morinda citrifolia L. fruit extracts: structural and optical analysis. J Mol Struct, 1231:129904.

[199]YunYJ, SongKB, 2013. Preparation and characterization of graphene oxide encapsulated gold nanoparticles. J Nanosci Nanotechnol, 13(11):7376-7380.

[200]ZandZ, KhakiPA, SalihiA, et al., 2019. Cerium oxide NPs mitigate the amyloid formation of α‍-synuclein and associated cytotoxicity. Int J Nanomedicine, 14:6989-7000.

[201]ZhangDY, LiuHK, LiCY, et al., 2020. Ceria nanozymes with preferential renal uptake for acute kidney injury alleviation. ACS Appl Mater Interfaces, 12(51):56830-56838.

[202]ZhangJ, WuZ, LiuT, et al., 2001. XANES study on the valence transitions in cerium oxide nanoparticles. J Synchrotron Radiat, 8(Pt 2):531-532.

[203]ZhangY, YangH, WeiDH, et al., 2021. Mitochondria-targeted nanoparticles in treatment of neurodegenerative diseases. Exploration, 1(3):20210115.

[204]ZhangYK, TangBT, XinY, et al., 2022. Nanobubbles loaded with carbon quantum dots for ultrasonic fluorescence dual detection. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(9):778-783.

[205]ZhaoCL, MaCY, LiWJ, et al., 2021. Differences in performance of immunosensors constructed based on CeO₂-simulating auxiliary enzymes. ACS Biomater Sci Eng, 7(3):1058-1064.

[206]ZhongYT, MaZR, ZhuSJ, et al., 2017. Boosting the down-shifting luminescence of rare-earth nanocrystals for biological imaging beyond 1500 nm. Nat Commun, 8:737.

[207]ZhouXH, WongLL, KarakotiAS, et al., 2011. Nanoceria inhibit the development and promote the regression of pathologic retinal neovascularization in the Vldlr knockout mouse. PLoS ONE, 6(2):e16733.

[208]ZhouXT, YouM, WangFH, et al., 2021. Multifunctional graphdiyne-cerium oxide nanozymes facilitate microRNA delivery and attenuate tumor hypoxia for highly efficient radiotherapy of esophageal cancer. Adv Mater, 33(24):2100556.

[209]ZidarM, RozmanP, Belko-ParkelK, et al., 2020. Control of viscosity in biopharmaceutical protein formulations. J Colloid Interface Sci, 580:308-317.

[210]ZuoL, FengQS, HanYY, et al., 2019. Therapeutic effect on experimental acute cerebral infarction is enhanced after nanoceria labeling of human umbilical cord mesenchymal stem cells. Ther Adv Neurol Disord, 12:1756286419859725.