{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T04:45:59Z","timestamp":1777351559836,"version":"3.51.4"},"reference-count":93,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T00:00:00Z","timestamp":1694649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Australian Research Council Discovery Project","award":["DP190102659"],"award-info":[{"award-number":["DP190102659"]}]},{"name":"Australian Research Council Discovery Project","award":["DP200100143"],"award-info":[{"award-number":["DP200100143"]}]},{"name":"Australian Research Council Discovery Project","award":["DE170100628"],"award-info":[{"award-number":["DE170100628"]}]},{"name":"Australian Postgraduate Award PhD scholarship","award":["DP190102659"],"award-info":[{"award-number":["DP190102659"]}]},{"name":"Australian Postgraduate Award PhD scholarship","award":["DP200100143"],"award-info":[{"award-number":["DP200100143"]}]},{"name":"Australian Postgraduate Award PhD scholarship","award":["DE170100628"],"award-info":[{"award-number":["DE170100628"]}]},{"name":"Australian Research Council Discovery Early Career Award","award":["DP190102659"],"award-info":[{"award-number":["DP190102659"]}]},{"name":"Australian Research Council Discovery Early Career Award","award":["DP200100143"],"award-info":[{"award-number":["DP200100143"]}]},{"name":"Australian Research Council Discovery Early Career Award","award":["DE170100628"],"award-info":[{"award-number":["DE170100628"]}]},{"name":"Yulgibar\/Dementia Australia","award":["DP190102659"],"award-info":[{"award-number":["DP190102659"]}]},{"name":"Yulgibar\/Dementia Australia","award":["DP200100143"],"award-info":[{"award-number":["DP200100143"]}]},{"name":"Yulgibar\/Dementia Australia","award":["DE170100628"],"award-info":[{"award-number":["DE170100628"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Nanoparticle-based magnetic contrast agents have opened the potential for magnetic resonance imaging (MRI) to be used for early non-invasive diagnosis of Alzheimer\u2019s disease (AD). Accumulation of amyloid pathology in the brain has shown association with cognitive decline and tauopathy; hence, it is an effective biomarker for the early detection of AD. The aim of this study was to develop a biocompatible magnetic nanoparticle targeted to amyloid beta (A\u03b2) plaques to increase the sensitivity of T2-weighted MRI for imaging of amyloid pathology in AD. We presented novel iron core-iron oxide nanoparticles stabilized with a dimercaptosuccinic acid coating and functionalized with an anti-A\u03b2 antibody. Nanoparticle biocompatibility and cellular internalization were evaluated in vitro in U-251 glioblastoma cells using cellular assays, proteomics, and transmission electron microscopy. Iron nanoparticles demonstrated no significant in vitro cytotoxicity, and electron microscopy results showed their movement through the endocytic cycle within the cell over a 24 h period. In addition, immunostaining and bio-layer interferometry confirmed the targeted nanoparticle\u2019s binding affinity to amyloid species. The iron nanoparticles demonstrated favourable MRI contrast enhancement; however, the addition of the antibody resulted in a reduction in the relaxivity of the particles. The present work shows promising preliminary results in the development of a targeted non-invasive method of early AD diagnosis using contrast-enhanced MRI.<\/jats:p>","DOI":"10.3390\/cells12182279","type":"journal-article","created":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T03:50:10Z","timestamp":1694749810000},"page":"2279","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Evaluation of Dimercaptosuccinic Acid-Coated Iron Nanoparticles Immunotargeted to Amyloid Beta as MRI Contrast Agents for the Diagnosis of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"12","author":[{"given":"Marina","family":"Ulanova","sequence":"first","affiliation":[{"name":"Centre for Healthy Brain Ageing, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucy","family":"Gloag","sequence":"additional","affiliation":[{"name":"Faculty of Science, School of Mathematical and Physical Science, University of Technology Sydney, Sydney, NSW 2007, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andre","family":"Bongers","sequence":"additional","affiliation":[{"name":"Mark Wainwright Analytical Centre, University of New South Wales, Sydney, NSW 2052, Australia"},{"name":"Faculty of Medicine, Prince of Wales Clinical School, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chul-Kyu","family":"Kim","sequence":"additional","affiliation":[{"name":"Centre for Healthy Brain Ageing, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong Thien Kim","family":"Duong","sequence":"additional","affiliation":[{"name":"School of Chemistry, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ha Na","family":"Kim","sequence":"additional","affiliation":[{"name":"Molecular Surface Interaction Laboratory, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5398-0597","authenticated-orcid":false,"given":"John Justin","family":"Gooding","sequence":"additional","affiliation":[{"name":"School of Chemistry, University of New South Wales, Sydney, NSW 2052, Australia"},{"name":"Australian Centre for NanoMedicine, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard D.","family":"Tilley","sequence":"additional","affiliation":[{"name":"Mark Wainwright Analytical Centre, University of New South Wales, Sydney, NSW 2052, Australia"},{"name":"School of Chemistry, University of New South Wales, Sydney, NSW 2052, Australia"},{"name":"Australian Centre for NanoMedicine, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna","family":"Biazik","sequence":"additional","affiliation":[{"name":"Mark Wainwright Analytical Centre, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wen","sequence":"additional","affiliation":[{"name":"Centre for Healthy Brain Ageing, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9595-3220","authenticated-orcid":false,"given":"Perminder S.","family":"Sachdev","sequence":"additional","affiliation":[{"name":"Centre for Healthy Brain Ageing, University of New South Wales, Sydney, NSW 2052, Australia"},{"name":"Neuropsychiatric Institute, Euroa Centre, Prince of Wales Hospital, Sydney, NSW 2031, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0497-5572","authenticated-orcid":false,"given":"Nady","family":"Braidy","sequence":"additional","affiliation":[{"name":"Centre for Healthy Brain Ageing, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,14]]},"reference":[{"key":"ref_1","unstructured":"WHO (2023, July 09). Dementia. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/dementia."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.3389\/fnins.2019.01154","article-title":"The Beta Amyloid Dysfunction (BAD) Hypothesis for Alzheimer\u2019s Disease. Hypothesis and Theory","volume":"13","author":"Hillen","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jalz.2014.02.004","article-title":"Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer\u2019s disease","volume":"11","author":"Blennow","year":"2015","journal-title":"Alzheimers Dement."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"203","DOI":"10.3233\/JAD-170793","article-title":"Reproducibility of Alzheimer\u2019s Disease Cerebrospinal Fluid-Biomarker Measurements under Clinical Routine Conditions","volume":"62","author":"Vogelgsang","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S236","DOI":"10.1016\/j.nima.2010.11.092","article-title":"Fundamental Limits of Spatial Resolution in PET","volume":"648","author":"Moses","year":"2011","journal-title":"Nucl. Instrum. Methods Phys. Res. Sect. A"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1016\/j.neurobiolaging.2011.03.009","article-title":"Gadolinium-staining reveals amyloid plaques in the brain of Alzheimer\u2019s transgenic mice","volume":"33","author":"Petiet","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4955","DOI":"10.1038\/s41598-017-05285-1","article-title":"Contrast-enhanced MR microscopy of amyloid plaques in five mouse models of amyloidosis and in human Alzheimer\u2019s disease brains","volume":"7","author":"Dudeffant","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"16185","DOI":"10.1038\/s41598-020-73233-7","article-title":"Pre-clinical dose-ranging efficacy, pharmacokinetics, tissue biodistribution, and toxicity of a targeted contrast agent for MRI of amyloid deposition in Alzheimer\u2019s disease","volume":"10","author":"Badachhape","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"18525","DOI":"10.1021\/acsami.1c01585","article-title":"Multimodal Theranostic Cyanine-Conjugated Gadolinium(III) Complex for In Vivo Imaging of Amyloid-\u03b2 in an Alzheimer\u2019s Disease Mouse Model","volume":"13","author":"Wang","year":"2021","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1909529","DOI":"10.1002\/adfm.201909529","article-title":"Amyloid-\u03b2 Oligomer-Targeted Gadolinium-Based NIR\/MR Dual-Modal Theranostic Nanoprobe for Alzheimer\u2019s Disease","volume":"30","author":"Wang","year":"2020","journal-title":"Adv. Funct. Mater."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/S0140-6736(00)02694-5","article-title":"Scleromyxoedema-like cutaneous diseases in renal-dialysis patients","volume":"356","author":"Cowper","year":"2000","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1093\/ndt\/gfk062","article-title":"Gadolinium--a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis?","volume":"21","author":"Grobner","year":"2006","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1681\/ASN.2006060601","article-title":"Nephrogenic Systemic Fibrosis: Suspected Causative Role of Gadodiamide Used for Contrast-Enhanced Magnetic Resonance Imaging","volume":"17","author":"Marckmann","year":"2006","journal-title":"Am. J. Nephrol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1148\/radiol.13131669","article-title":"High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: Relationship with increasing cumulative dose of a gadolinium-based contrast material","volume":"270","author":"Kanda","year":"2014","journal-title":"Radiology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1097\/RLI.0000000000000252","article-title":"Macrocyclic and Other Non-Group 1 Gadolinium Contrast Agents Deposit Low Levels of Gadolinium in Brain and Bone Tissue: Preliminary Results From 9 Patients With Normal Renal Function","volume":"51","author":"Murata","year":"2016","journal-title":"Investig. Radiol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Yeo, S.K., Shepelytskyi, Y., Grynko, V., and Albert, M.S. (2020). Molecular Imaging of Fluorinated Probes for Tau Protein and Amyloid-\u03b2 Detection. Molecules, 25.","DOI":"10.3390\/molecules25153413"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Yanagisawa, D., Ibrahim, N.F., Taguchi, H., Morikawa, S., Tomiyama, T., and Tooyama, I. (2021). Fluorine-19 Magnetic Resonance Imaging for Detection of Amyloid \u03b2 Oligomers Using a Keto Form of Curcumin Derivative in a Mouse Model of Alzheimer\u2019s Disease. Molecules, 26.","DOI":"10.3390\/molecules26051362"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1021\/acssensors.8b01216","article-title":"In Vivo and In Vitro Monitoring of Amyloid Aggregation via BSA@FGQDs Multimodal Probe","volume":"4","author":"Yousaf","year":"2019","journal-title":"ACS Sens."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"725","DOI":"10.2217\/nnm-2019-0316","article-title":"Nanoparticles as contrast agents for the diagnosis of Alzheimer\u2019s disease: A systematic review","volume":"15","author":"Ulanova","year":"2020","journal-title":"Nanomedicine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.msec.2014.01.005","article-title":"Synthesis of superparamagnetic iron oxide nanoparticles coated with a DDNP-carboxyl derivative for in vitro magnetic resonance imaging of Alzheimer\u2019s disease","volume":"37","author":"Zhou","year":"2014","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.crad.2014.09.019","article-title":"The detection of \u03b2-amyloid plaques in an Alzheimer\u2019s disease rat model with DDNP-SPIO","volume":"70","author":"Zhang","year":"2015","journal-title":"Clin. Radiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5300804","DOI":"10.1109\/TMAG.2017.2715841","article-title":"Magnetic Fluorescent Nanoparticles Binding to Amyloid-Beta Peptide: Silica-Coated, Thioflavin-T Functionalized Iron Oxide","volume":"53","author":"Tsolakis","year":"2017","journal-title":"IEEE Trans. Magn."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/mrm.10529","article-title":"Detection of Alzheimer\u2019s amyloid in transgenic mice using magnetic resonance microimaging","volume":"50","author":"Wadghiri","year":"2003","journal-title":"Magn. Reson. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1016\/j.neuroimage.2011.01.023","article-title":"Detection of amyloid plaques targeted by USPIO-A\u03b21-42 in Alzheimer\u2019s disease transgenic mice using magnetic resonance microimaging","volume":"55","author":"Yang","year":"2011","journal-title":"Neuroimage"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Wadghiri, Y.Z., Li, J., Wang, J., Hoang, D.M., Sun, Y., Xu, H., Tsui, W., Li, Y., Boutajangout, A., and Wang, A. (2013). Detection of amyloid plaques targeted by bifunctional USPIO in Alzheimer\u2019s disease transgenic mice using magnetic resonance microimaging. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0057097"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"927","DOI":"10.2147\/IJN.S351830","article-title":"Amyloid Plaque Imaging with a Targeted MRI Contrast Agent in a Transgenic Mouse Model of Alzheimer\u2019s Disease","volume":"17","author":"Xiong","year":"2022","journal-title":"Int. J. Nanomed."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/nnano.2014.254","article-title":"Towards non-invasive diagnostic imaging of early-stage Alzheimer\u2019s disease","volume":"10","author":"Viola","year":"2015","journal-title":"Nat. Nanotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6429","DOI":"10.1166\/jnn.2015.11296","article-title":"Preparation of Amyloid Immuno-Nanoparticles as Potential MRI Contrast Agents for Alzheimer\u2019s Disease Diagnosis","volume":"15","author":"Yin","year":"2015","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"191","DOI":"10.3233\/JAD-131031","article-title":"Optical and SPION-enhanced MR imaging shows that trans-stilbene inhibitors of NF-\u03baB concomitantly lower Alzheimer\u2019s disease plaque formation and microglial activation in A\u03b2PP\/PS-1 transgenic mouse brain","volume":"40","author":"Solberg","year":"2014","journal-title":"J. Alzheimers Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"349","DOI":"10.3233\/JAD-121171","article-title":"SPION-enhanced magnetic resonance imaging of Alzheimer\u2019s disease plaques in A\u03b2PP\/PS-1 transgenic mouse brain","volume":"34","author":"Sillerud","year":"2013","journal-title":"J. Alzheimers Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1002\/jmri.25563","article-title":"Superparamagnetic nanoparticle-enhanced MRI of Alzheimer\u2019s disease plaques and activated microglia in 3X transgenic mouse brains: Contrast optimization","volume":"46","author":"Tafoya","year":"2017","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4919","DOI":"10.2147\/IJN.S240953","article-title":"Multifunctional Superparamagnetic Iron Oxide Nanoparticles Conjugated with A\u03b2 Oligomer-Specific scFv Antibody and Class A Scavenger Receptor Activator Show Early Diagnostic Potentials for Alzheimer\u2019s Disease","volume":"15","author":"Liu","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"103748","DOI":"10.1016\/j.arabjc.2022.103748","article-title":"Iron oxide nanoparticles-loaded hyaluronic acid nanogels for MRI-aided Alzheimer\u2019s disease theranostics","volume":"15","author":"Chen","year":"2022","journal-title":"Arab. J. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2100019","DOI":"10.1002\/anbr.202100019","article-title":"Lipocalin-Type Prostaglandin d Synthase Conjugates as Magnetic Resonance Imaging Contrast Agents for Detecting Amyloid \u03b2-Rich Regions in the Brain of Live Alzheimer\u2019s Disease Mice","volume":"1","author":"Sharma","year":"2021","journal-title":"Adv. Nanobiomed Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3504","DOI":"10.1039\/C9CC08972A","article-title":"Zero valent iron core-iron oxide shell nanoparticles as small magnetic particle imaging tracers","volume":"56","author":"Gloag","year":"2020","journal-title":"Chem. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1904385","DOI":"10.1002\/adma.201904385","article-title":"Advances in the Application of Magnetic Nanoparticles for Sensing","volume":"31","author":"Gloag","year":"2019","journal-title":"Adv Mater"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.nano.2013.11.010","article-title":"Efficient and safe internalization of magnetic iron oxide nanoparticles: Two fundamental requirements for biomedical applications","volume":"10","author":"Calero","year":"2014","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuint.2014.12.005","article-title":"Accumulation of iron oxide nanoparticles by cultured primary neurons","volume":"81","author":"Petters","year":"2015","journal-title":"Neurochem. Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3682","DOI":"10.1038\/s41598-018-22018-0","article-title":"Potential use of superparamagnetic iron oxide nanoparticles for in vitro and in vivo bioimaging of human myoblasts","volume":"8","author":"Wierzbinski","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s12951-016-0213-x","article-title":"Labeling mesenchymal cells with DMSA-coated gold and iron oxide nanoparticles: Assessment of biocompatibility and potential applications","volume":"14","author":"Silva","year":"2016","journal-title":"J. Nanobiotechnology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1186\/s12974-020-01976-1","article-title":"Neuroprotective effects of verbascoside against Alzheimer\u2019s disease via the relief of endoplasmic reticulum stress in A\u03b2-exposed U251 cells and APP\/PS1 mice","volume":"17","author":"Wang","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/s41392-021-00748-4","article-title":"A novel missense variant in ACAA1 contributes to early-onset Alzheimer\u2019s disease, impairs lysosomal function, and facilitates amyloid-\u03b2 pathology and cognitive decline","volume":"6","author":"Luo","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"108","DOI":"10.3892\/mmr.2020.11747","article-title":"Neuroprotective effect of emodin against Alzheimer\u2019s disease via Nrf2 signaling in U251 cells and APP\/PS1 mice","volume":"23","author":"Li","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.nurt.2010.07.006","article-title":"Functions of astrocytes and their potential as therapeutic targets","volume":"7","author":"Kimelberg","year":"2010","journal-title":"Neurotherapeutics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"145101","DOI":"10.1088\/0957-4484\/22\/14\/145101","article-title":"Uptake of dimercaptosuccinate-coated magnetic iron oxide nanoparticles by cultured brain astrocytes","volume":"22","author":"Geppert","year":"2011","journal-title":"Nanotechnology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/0165-1161(75)90046-1","article-title":"Methods for detecting carcinogens and mutagens with the salmonella\/mammalian-microsome mutagenicity test","volume":"31","author":"Ames","year":"1975","journal-title":"Mutat. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1021\/acs.jproteome.0c00670","article-title":"Extending the Depth of Human Plasma Proteome Coverage Using Simple Fractionation Techniques","volume":"20","author":"Kaur","year":"2021","journal-title":"J. Proteome Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/nmeth.3901","article-title":"The Perseus computational platform for comprehensive analysis of (prote)omics data","volume":"13","author":"Tyanova","year":"2016","journal-title":"Nat. Methods"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1152\/physrev.2001.81.2.741","article-title":"Alzheimer\u2019s disease: Genes, proteins, and therapy","volume":"81","author":"Selkoe","year":"2001","journal-title":"Physiol. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"eaaz6014","DOI":"10.1126\/sciadv.aaz6014","article-title":"Complete aggregation pathway of amyloid \u03b2 (1-40) and (1-42) resolved on an atomically clean interface","volume":"6","author":"Nirmalraj","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s40263-016-0405-9","article-title":"Crossing the Blood\u2013Brain Barrier: Recent Advances in Drug Delivery to the Brain","volume":"31","author":"Patel","year":"2017","journal-title":"CNS Drugs"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"249","DOI":"10.3233\/JAD-200715","article-title":"Anti-A\u03b2 Antibody Aducanumab Regulates the Proteome of Senile Plaques and Closely Surrounding Tissue in a Transgenic Mouse Model of Alzheimer\u2019s Disease","volume":"79","author":"Bastrup","year":"2021","journal-title":"J. Alzheimers Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1002\/hipo.22676","article-title":"A novel antibody targeting sequence 31\u201335 in amyloid \u03b2 protein attenuates Alzheimer\u2019s disease-related neuronal damage","volume":"27","author":"Cheng","year":"2017","journal-title":"Hippocampus"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/j.1471-4159.2012.07754.x","article-title":"Intravenous immunoglobulin protects neurons against amyloid beta-peptide toxicity and ischemic stroke by attenuating multiple cell death pathways","volume":"122","author":"Widiapradja","year":"2012","journal-title":"J. Neurochem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s12951-015-0073-9","article-title":"Characterization of interaction of magnetic nanoparticles with breast cancer cells","volume":"13","author":"Calero","year":"2015","journal-title":"J. Nanobiotechnology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1007\/s11051-021-05249-7","article-title":"Transmission electron microscopy and flow cytometry study of cellular uptake of unmodified Pr3+:LaF3 nanoparticles in dynamic","volume":"23","author":"Pudovkin","year":"2021","journal-title":"J. Nanopart Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"35906","DOI":"10.1021\/acsami.3c05555","article-title":"Interaction of Iron Oxide Nanoparticles with Macrophages Is Influenced Distinctly by \u201cSelf\u201d and \u201cNon-Self\u201d Biological Identities","volume":"15","author":"Portilla","year":"2023","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"11476","DOI":"10.1021\/acs.chemrev.7b00194","article-title":"Form Follows Function: Nanoparticle Shape and Its Implications for Nanomedicine","volume":"117","author":"Kinnear","year":"2017","journal-title":"Chem. Rev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1007\/s00249-001-0200-4","article-title":"Magnetophoresis and ferromagnetic resonance of magnetically labeled cells","volume":"31","author":"Wilhelm","year":"2002","journal-title":"Eur. Biophys. J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1002\/smll.201102356","article-title":"Thirty-femtogram detection of iron in mammalian cells","volume":"8","author":"Galimard","year":"2012","journal-title":"Small"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.1016\/j.biomaterials.2011.01.008","article-title":"Dimercaptosuccinic acid-coated magnetite nanoparticles for magnetically guided in vivo delivery of interferon gamma for cancer immunotherapy","volume":"32","author":"Cabrera","year":"2011","journal-title":"Biomaterials"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"115103","DOI":"10.1088\/0957-4484\/20\/11\/115103","article-title":"The influence of surface functionalization on the enhanced internalization of magnetic nanoparticles in cancer cells","volume":"20","author":"Villanueva","year":"2009","journal-title":"Nanotechnology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4402","DOI":"10.1039\/c1nr10778j","article-title":"Nanomagnetism reveals the intracellular clustering of iron oxide nanoparticles in the organism","volume":"3","author":"Levy","year":"2011","journal-title":"Nanoscale"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"754721","DOI":"10.1155\/2014\/754721","article-title":"A proteomics analysis to evaluate cytotoxicity in NRK-52E cells caused by unmodified Nano-Fe3O4","volume":"2014","author":"Lin","year":"2014","journal-title":"Sci. World J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1080\/17435390.2019.1621399","article-title":"Investigating the toxic effects induced by iron oxide nanoparticles on neuroblastoma cell line: An integrative study combining cytotoxic, genotoxic and proteomic tools","volume":"13","author":"Askri","year":"2019","journal-title":"Nanotoxicology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"9960","DOI":"10.1039\/C7NR02196H","article-title":"Functional insights into the cellular response triggered by a bile-acid platinum compound conjugated to biocompatible ferric nanoparticles using quantitative proteomic approaches. 10.1039\/C7NR02196H","volume":"9","author":"Murillo","year":"2017","journal-title":"Nanoscale"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"10077","DOI":"10.1021\/nn502754c","article-title":"Mass Spectrometry and Imaging Analysis of Nanoparticle-Containing Vesicles Provide a Mechanistic Insight into Cellular Trafficking","volume":"8","author":"Hofmann","year":"2014","journal-title":"ACS Nano"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Luo, T., Gao, J., Lin, N., and Wang, J. (2020). Effects of Two Kinds of Iron Nanoparticles as Reactive Oxygen Species Inducer and Scavenger on the Transcriptomic Profiles of Two Human Leukemia Cells with Different Stemness. Nanomaterials, 10.","DOI":"10.3390\/nano10101951"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1903323","DOI":"10.1002\/advs.201903323","article-title":"Iron Oxide Nanoparticles as Autophagy Intervention Agents Suppress Hepatoma Growth by Enhancing Tumoricidal Autophagy","volume":"7","author":"Xie","year":"2020","journal-title":"Adv. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"705","DOI":"10.2217\/nnm.11.148","article-title":"Degradation of superparamagnetic iron oxide nanoparticle-induced ferritin by lysosomal cathepsins and related immune response","volume":"7","author":"Laskar","year":"2012","journal-title":"Nanomedicine"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Laurent, S., Burtea, C., Thirifays, C., H\u00e4feli, U.O., and Mahmoudi, M. (2012). Crucial Ignored Parameters on Nanotoxicology: The Importance of Toxicity Assay Modifications and \u201cCell Vision\u201d. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0029997"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/1477-5956-6-29","article-title":"Dramatic down-regulation of oxidoreductases in human hepatocellular carcinoma hepG2 cells: Proteomics and gene ontology unveiling new frontiers in cancer enzymology","volume":"6","author":"Ngoka","year":"2008","journal-title":"Proteome Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S0945-053X(00)00084-6","article-title":"Heparin-binding proteins HB-GAM (pleiotrophin) and amphoterin in the regulation of cell motility","volume":"19","author":"Rauvala","year":"2000","journal-title":"Matrix Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"6079","DOI":"10.1038\/sj.onc.1209628","article-title":"Cortactin underpins CD44-promoted invasion and adhesion of breast cancer cells to bone marrow endothelial cells","volume":"25","author":"Hill","year":"2006","journal-title":"Oncogene"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4884","DOI":"10.1039\/C4NR06594H","article-title":"Manipulating directional cell motility using intracellular superparamagnetic nanoparticles","volume":"7","author":"Bradshaw","year":"2015","journal-title":"Nanoscale"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Diana, V., Bossolasco, P., Moscatelli, D., Silani, V., and Cova, L. (2013). Dose Dependent Side Effect of Superparamagnetic Iron Oxide Nanoparticle Labeling on Cell Motility in Two Fetal Stem Cell Populations. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0078435"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1002\/smll.201000763","article-title":"Intracellular nanoparticle coating stability determines nanoparticle diagnostics efficacy and cell functionality","volume":"6","author":"Soenen","year":"2010","journal-title":"Small"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/mrm.24216","article-title":"Cell motility of neural stem cells is reduced after SPIO-labeling, which is mitigated after exocytosis","volume":"69","author":"Kshitiz","year":"2013","journal-title":"Magn. Reson. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1038\/icb.2011.20","article-title":"Macropinocytosis: An endocytic pathway for internalising large gulps","volume":"89","author":"Lim","year":"2011","journal-title":"Immunol. Cell Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1002\/smll.200902084","article-title":"High intracellular iron oxide nanoparticle concentrations affect cellular cytoskeleton and focal adhesion kinase-mediated signaling","volume":"6","author":"Soenen","year":"2010","journal-title":"Small"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"10436","DOI":"10.1039\/D1NR00901J","article-title":"Imaging of nanoparticle uptake and kinetics of intracellular trafficking in individual cells","volume":"13","author":"Vtyurina","year":"2021","journal-title":"Nanoscale"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Kamentseva, R., Kosheverova, V., Kharchenko, M., Zlobina, M., Salova, A., Belyaeva, T., Nikolsky, N., and Kornilova, E. (2020). Functional cycle of EEA1-positive early endosome: Direct evidence for pre-existing compartment of degradative pathway. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0232532"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/ncb2970","article-title":"Galectin-3 drives glycosphingolipid-dependent biogenesis of clathrin-independent carriers","volume":"16","author":"Lakshminarayan","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s40478-019-0660-3","article-title":"The APMAP interactome reveals new modulators of APP processing and beta-amyloid production that are altered in Alzheimer\u2019s disease","volume":"7","author":"Gerber","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13578-017-0165-3","article-title":"Isocitrate dehydrogenases in physiology and cancer: Biochemical and molecular insight","volume":"7","year":"2017","journal-title":"Cell Biosci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1096\/fj.02-1131fje","article-title":"The expression and functional characterization of ABCG2 in brain endothelial cells and vessels","volume":"17","author":"Zhang","year":"2003","journal-title":"Faseb J."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3389\/fphar.2012.00077","article-title":"Heme cytotoxicity and the pathogenesis of immune-mediated inflammatory diseases","volume":"3","author":"Larsen","year":"2012","journal-title":"Front. Pharmacol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"12425","DOI":"10.1021\/acsnano.5b05783","article-title":"Parallel Comparative Studies on Mouse Toxicity of Oxide Nanoparticle- and Gadolinium-Based T1 MRI Contrast Agents","volume":"9","author":"Chen","year":"2015","journal-title":"ACS Nano"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.biocel.2011.10.019","article-title":"Endoplasmic reticulum stress signaling is involved in silver nanoparticles-induced apoptosis","volume":"44","author":"Zhang","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"101","DOI":"10.4161\/auto.22266","article-title":"Interplay between apoptotic and autophagy pathways after exposure to cerium dioxide nanoparticles in human monocytes","volume":"9","author":"Hussain","year":"2013","journal-title":"Autophagy"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"58","DOI":"10.3892\/ol.2021.13176","article-title":"Function of BCLAF1 in human disease","volume":"23","author":"Yu","year":"2022","journal-title":"Oncol. Lett."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s12987-020-00230-3","article-title":"A blood\u2013brain barrier overview on structure, function, impairment, and biomarkers of integrity","volume":"17","author":"Kadry","year":"2020","journal-title":"Fluids Barriers CNS"},{"key":"ref_93","first-page":"1709","article-title":"Preliminary biocompatibility investigation of magnetic albumin nanosphere designed as a potential versatile drug delivery system","volume":"6","author":"Estevanato","year":"2011","journal-title":"Int. J. Nanomed."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/18\/2279\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:51:08Z","timestamp":1760129468000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/18\/2279"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,14]]},"references-count":93,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["cells12182279"],"URL":"https:\/\/doi.org\/10.3390\/cells12182279","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,14]]}}}