{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:07:27Z","timestamp":1789621647112,"version":"build-2803163510"},"reference-count":124,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002468","name":"Dong-A University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002468","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/03qvtpc38","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>Graphene quantum dots (GQDs) constitute the zero-dimensional family of carbon nanomaterials, combining efficient penetration of the blood\u2013brain barrier (BBB) with precisely controllable surface chemistry, and have drawn attention as theragnostic platforms that carry both diagnosis and therapy in a single particle. Although various neurodegenerative diseases each arise from a different causal protein, they converge on shared pathology: aberrant accumulation of neuronal proteins and chronic neuroinflammation driven by pathological activation of glial cells such as microglia and astrocytes. GQDs modulate aggregation through monomer capture that delays nucleation, the blockade of growing fibril tips, and the penetration and disassembly of mature fibrils, all of which have been verified against various protein aggregation models. Beyond aggregation control, heteroatom doping and surface functionalization design allow GQDs to scavenge reactive oxygen species (ROS) and adjust autophagic pathways, attenuating markers of pathological microglial activation. Tunable emission simultaneously enables imaging of pathological burden and high-sensitivity detection of fluid biomarkers, supporting integration of therapeutic and diagnostic functions. GQD bioactivity, however, is inherently double-edged: depending on composition and concentration, the same materials can trigger mitochondrial oxidative stress and ferroptosis rather than exerting antioxidant action, as observed in microglia and macrophages. Therefore, key challenges remain separating anti-inflammatory efficacy from toxicity through precise surface functionalization, ensuring batch-to-batch reproducibility, establishing standardized physicochemical reporting, and quantitatively delineating the therapeutic window.<\/jats:p>","DOI":"10.3390\/nano16181158","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T09:31:57Z","timestamp":1789464717000},"page":"1158","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Graphene Quantum Dots in Neurodegeneration: Protein Aggregation and the Microglial State as Therapeutic Targets"],"prefix":"10.3390","volume":"16","author":[{"given":"Hanna","family":"Jeong","sequence":"first","affiliation":[{"name":"Department of Translational Biomedical Sciences, Graduate School of Dong-A University, Busan 49201, Republic of Korea"},{"name":"Department of Pharmacology, College of Medicine, Dong-A University, Busan 49201, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedical Sciences, Graduate School of Dong-A University, Busan 49201, Republic of Korea"},{"name":"Department of Pharmacology, College of Medicine, Dong-A University, Busan 49201, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seoyu","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedical Sciences, Graduate School of Dong-A University, Busan 49201, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3074-859X","authenticated-orcid":false,"given":"Je Min","family":"Yoo","sequence":"additional","affiliation":[{"name":"Chaperone Ventures LLC, Los Angeles, CA 90010, USA"},{"name":"SmartinBio Inc., Cheongju 28160, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong Seok","family":"Choi","sequence":"additional","affiliation":[{"name":"Graphene Research Center, Advanced Institute of Convergence Technology, Suwon 16229, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Ho","family":"Kwon","sequence":"additional","affiliation":[{"name":"Biochemistry, Cellular and Molecular Biology Graduate Program, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heehong","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Interdisciplinary Program in Neuroscience, Seoul National University, Seoul 08826, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minyeop","family":"Nahm","sequence":"additional","affiliation":[{"name":"Dementia Research Group, Korea Brain Research Institute, Daegu 41062, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7493-0935","authenticated-orcid":false,"given":"Donghoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedical Sciences, Graduate School of Dong-A University, Busan 49201, Republic of Korea"},{"name":"Department of Pharmacology, College of Medicine, Dong-A University, Busan 49201, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1021\/np068054v","article-title":"Natural products as sources of new drugs over the last 25 years","volume":"70","author":"Newman","year":"2007","journal-title":"J. Nat. Prod."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3670","DOI":"10.1016\/j.bbagen.2013.02.008","article-title":"Natural products: A continuing source of novel drug leads","volume":"1830","author":"Cragg","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural Products as Sources of New Drugs over the Nearly Four Decades from 01\/1981 to 09\/2019","volume":"83","author":"Newman","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/B978-0-12-416020-0.00008-5","article-title":"Nanobiotechnology and personalized medicine","volume":"104","author":"Jain","year":"2011","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1189\/jlb.0205074","article-title":"Nanotechnology for the biologist","volume":"78","author":"McNeil","year":"2005","journal-title":"J. Leukoc. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1186\/s12951-022-01477-8","article-title":"Nanoparticle classification, physicochemical properties, characterization, and applications: A comprehensive review for biologists","volume":"20","author":"Joudeh","year":"2022","journal-title":"J. Nanobiotechnol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1016\/j.ymthe.2017.04.026","article-title":"Nanomaterial-Enabled Cancer Therapy","volume":"25","author":"Quader","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1039\/D5LP00154D","article-title":"Nanocarrier strategies for deep tumour penetration","volume":"3","author":"Zhang","year":"2025","journal-title":"RSC Appl. Polym."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Paramasivam, G., Palem, V.V., Sundaram, T., Sundaram, V., Kishore, S.C., and Bellucci, S. (2021). Nanomaterials: Synthesis and Applications in Theranostics. Nanomaterials, 11.","DOI":"10.3390\/nano11123228"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1021\/acs.nanolett.9b00472","article-title":"Gold Nanoparticle-Integrated Scaffolds for Tissue Engineering and Regenerative Medicine","volume":"19","author":"Yadid","year":"2019","journal-title":"Nano Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9559","DOI":"10.1021\/acs.chemrev.9b00099","article-title":"Nanocarbons for Biology and Medicine: Sensing, Imaging, and Drug Delivery","volume":"119","author":"Panwar","year":"2019","journal-title":"Chem. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Maiti, D., Tong, X., Mou, X., and Yang, K. (2019). Carbon-Based Nanomaterials for Biomedical Applications: A Recent Study. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.01401"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"119701","DOI":"10.1016\/j.ijpharm.2020.119701","article-title":"Carbon nanostructures: The drug and the delivery system for brain disorders","volume":"587","author":"Henna","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1039\/D4MH01256A","article-title":"Application of carbon-based nanomaterials in Alzheimer\u2019s disease","volume":"12","author":"Bai","year":"2025","journal-title":"Mater. Horiz."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1177\/13872877251407702","article-title":"Carbon nanomaterials for tau targeting in Alzheimer\u2019s disease: Theranostic strategies and clinical prospects","volume":"109","author":"Muthuramalingam","year":"2026","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6858","DOI":"10.1021\/nn402043c","article-title":"In vivo biodistribution and toxicology of carboxylated graphene quantum dots","volume":"7","author":"Nurunnabi","year":"2013","journal-title":"ACS Nano"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1021\/acs.chemrestox.0c00050","article-title":"Neurotoxicology of Nanomaterials","volume":"33","author":"Boyes","year":"2020","journal-title":"Chem. Res. Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.tibtech.2016.08.011","article-title":"Biological Identity of Nanoparticles In Vivo: Clinical Implications of the Protein Corona","volume":"35","author":"Caracciolo","year":"2017","journal-title":"Trends Biotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Akhter, H., Khalilullah, H., Gupta, M., Alfaleh, M.A., Alhakamy, N.A., Riadi, Y., and Shadab, M. (2021). Impact of Protein Corona on the Biological Identity of Nanomedicine: Understanding the Fate of Nanomaterials in the Biological Milieu. Biomedicines, 9.","DOI":"10.3390\/biomedicines9101496"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1038\/s41565-024-01754-7","article-title":"A translational framework to DELIVER nanomedicines to the clinic","volume":"19","author":"Joyce","year":"2024","journal-title":"Nat. Nanotechnol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/318162a0","article-title":"C60: Buckminsterfullerene","volume":"318","author":"Kroto","year":"1985","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/347354a0","article-title":"Solid C60: A new form of carbon","volume":"347","author":"Lamb","year":"1990","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/354056a0","article-title":"Helical microtubules of graphitic carbon","volume":"354","author":"Iijima","year":"1991","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s12274-009-9009-8","article-title":"Carbon nanotubes in biology and medicine: In vitro and in vivo detection, imaging and drug delivery","volume":"2","author":"Liu","year":"2009","journal-title":"Nano Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1126\/science.1102896","article-title":"Electric field effect in atomically thin carbon films","volume":"306","author":"Novoselov","year":"2004","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1186\/s12951-020-00698-z","article-title":"Synthesis of graphene quantum dots and their applications in drug delivery","volume":"18","author":"Zhao","year":"2020","journal-title":"J. Nanobiotechnol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1126\/science.1154663","article-title":"Chaotic Dirac Billiard in Graphene Quantum Dots","volume":"320","author":"Ponomarenko","year":"2008","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1002\/adma.200902825","article-title":"Hydrothermal Route for Cutting Graphene Sheets into Blue-Luminescent Graphene Quantum Dots","volume":"22","author":"Pan","year":"2010","journal-title":"Adv. Mater."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1021\/nl2038979","article-title":"Graphene quantum dots derived from carbon fibers","volume":"12","author":"Peng","year":"2012","journal-title":"Nano Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7794","DOI":"10.1039\/C6NR00605A","article-title":"Mechanism for excitation-dependent photoluminescence from graphene quantum dots and other graphene oxide derivates: Consensus, debates and challenges","volume":"8","author":"Gan","year":"2016","journal-title":"Nanoscale"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"11988","DOI":"10.1039\/C4NR02365J","article-title":"Edge-enriched graphene quantum dots for enhanced photo-luminescence and supercapacitance","volume":"6","author":"Hassan","year":"2014","journal-title":"Nanoscale"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4015","DOI":"10.1039\/c3nr33849e","article-title":"Focusing on luminescent graphene quantum dots: Current status and future perspectives","volume":"5","author":"Li","year":"2013","journal-title":"Nanoscale"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e2102683","DOI":"10.1002\/smll.202102683","article-title":"Synthesis, Applications, and Prospects of Graphene Quantum Dots: A Comprehensive Review","volume":"18","author":"Ghaffarkhah","year":"2022","journal-title":"Small"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6858","DOI":"10.1039\/c1cc11122a","article-title":"Strongly green-photoluminescent graphene quantum dots for bioimaging applications","volume":"47","author":"Zhu","year":"2011","journal-title":"Chem. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Younis, M.R., He, G., Lin, J., and Huang, P. (2020). Recent Advances on Graphene Quantum Dots for Bioimaging Applications. Front. Chem., 8.","DOI":"10.3389\/fchem.2020.00424"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1038\/nbt1340","article-title":"Renal clearance of quantum dots","volume":"25","author":"Choi","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e1904362","DOI":"10.1002\/adma.201904362","article-title":"Graphene Quantum Dots and Their Applications in Bioimaging, Biosensing, and Therapy","volume":"33","author":"Chung","year":"2021","journal-title":"Adv. Mater."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Perini, G., Palmieri, V., Ciasca, G., De Spirito, M., and Papi, M. (2020). Unravelling the Potential of Graphene Quantum Dots in Biomedicine and Neuroscience. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103712"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4307","DOI":"10.1039\/D4TB00255E","article-title":"Innovative approaches for cancer treatment: Graphene quantum dots for photodynamic and photothermal therapies","volume":"12","author":"Zarepour","year":"2024","journal-title":"J. Mater. Chem. B"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1038\/s41565-018-0179-y","article-title":"Graphene quantum dots prevent \u03b1-synucleinopathy in Parkinson\u2019s disease","volume":"13","author":"Kim","year":"2018","journal-title":"Nat. Nanotechnol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e2304497","DOI":"10.1002\/smll.202304497","article-title":"From Pristine to Heteroatom-Doped Graphene Quantum Dots: An Essential Review and Prospects for Future Research","volume":"19","author":"Im","year":"2023","journal-title":"Small"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1007\/s00604-025-07683-z","article-title":"Reproducibility roadblocks and standardization in carbon dot synthesis: A critical review of current practices, challenges, and future directions","volume":"192","author":"Jing","year":"2025","journal-title":"Mikrochim. Acta"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kn\u00e1pek, A., Dallaev, R., Burda, D., Sobola, D., Allaham, M.M., Hor\u00e1\u010dek, M., Kaspar, P., Mat\u011bjka, M., and Mousa, M.S. (2020). Field Emission Properties of Polymer Graphite Tips Prepared by Membrane Electrochemical Etching. Nanomaterials, 10.","DOI":"10.3390\/nano10071294"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.jcis.2020.11.102","article-title":"A graphene oxide Cookbook: Exploring chemical and colloidal properties as a function of synthesis parameters","volume":"588","author":"An","year":"2021","journal-title":"J. Colloid Interface Sci."},{"key":"ref_45","unstructured":"GBD 2019 Dementia Forecasting Collaborators (2022). Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: An analysis for the Global Burden of Disease Study 2019. Lancet Public Health, 7, e105\u2013e125."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S1474-4422(19)30411-9","article-title":"The global burden of neurological disorders: Translating evidence into policy","volume":"19","author":"Feigin","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.arr.2019.01.012","article-title":"The prion-like spreading of \u03b1-synuclein: From in vitro to in vivo models of Parkinson\u2019s disease","volume":"50","author":"Vargas","year":"2019","journal-title":"Ageing Res. Rev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s12974-022-02421-1","article-title":"ALS monocyte-derived microglia-like cells reveal cytoplasmic TDP-43 accumulation, DNA damage, and cell-specific impairment of phagocytosis associated with disease progression","volume":"19","author":"Quek","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Jan, A., Gon\u00e7alves, N.P., Vaegter, C.B., Jensen, P.H., and Ferreira, N. (2021). The Prion-Like Spreading of Alpha-Synuclein in Parkinson\u2019s Disease: Update on Models and Hypotheses. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158338"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Teleanu, D.M., Niculescu, A.G., Lungu, I.I., Radu, C.I., Vlad\u00e2cenco, O., Roza, E., Cost\u0103chescu, B., Grumezescu, A.M., and Teleanu, R.I. (2022). An Overview of Oxidative Stress, Neuroinflammation, and Neurodegenerative Diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23115938"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Isik, S., Yeman Kiyak, B., Akbayir, R., Seyhali, R., and Arpaci, T. (2023). Microglia Mediated Neuroinflammation in Parkinson\u2019s Disease. Cells, 12.","DOI":"10.3390\/cells12071012"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3458","DOI":"10.1016\/j.neuron.2022.10.020","article-title":"Microglia states and nomenclature: A field at its crossroads","volume":"110","author":"Paolicelli","year":"2022","journal-title":"Neuron"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Li, Y., Xia, Y., Yin, S., Wan, F., Hu, J., Kou, L., Sun, Y., Wu, J., Zhou, Q., and Huang, J. (2021). Targeting Microglial \u03b1-Synuclein\/TLRs\/NF-\u03baB\/NLRP3 Inflammasome Axis in Parkinson\u2019s Disease. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.719807"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1146\/annurev-neuro-061010-113810","article-title":"The complement system: An unexpected role in synaptic pruning during development and disease","volume":"35","author":"Stephan","year":"2012","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.cell.2017.05.018","article-title":"A Unique Microglia Type Associated with Restricting Development of Alzheimer\u2019s Disease","volume":"169","author":"Spinrad","year":"2017","journal-title":"Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/s41591-019-0695-9","article-title":"Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer\u2019s disease","volume":"26","author":"Zhou","year":"2020","journal-title":"Nat. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/s00401-020-02200-3","article-title":"APOE and TREM2 regulate amyloid-responsive microglia in Alzheimer\u2019s disease","volume":"140","author":"Nguyen","year":"2020","journal-title":"Acta Neuropathol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1038\/s43587-022-00281-1","article-title":"Complement C1q-dependent excitatory and inhibitory synapse elimination by astrocytes and microglia in Alzheimer\u2019s disease mouse models","volume":"2","author":"Dejanovic","year":"2022","journal-title":"Nat. Aging"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1038\/s41467-021-22301-1","article-title":"Loss of microglial SIRP\u03b1 promotes synaptic pruning in preclinical models of neurodegeneration","volume":"12","author":"Ding","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"eadf0141","DOI":"10.1126\/scitranslmed.adf0141","article-title":"The neuronal pentraxin Nptx2 regulates complement activity and restrains microglia-mediated synapse loss in neurodegeneration","volume":"15","author":"Zhou","year":"2023","journal-title":"Sci. Transl. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/s41591-018-0051-5","article-title":"Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson\u2019s disease","volume":"24","author":"Yun","year":"2018","journal-title":"Nat. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1038\/s41593-024-01600-y","article-title":"Xenografted human microglia display diverse transcriptomic states in response to Alzheimer\u2019s disease-related amyloid-\u03b2 pathology","volume":"27","author":"Mancuso","year":"2024","journal-title":"Nat. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1007\/s00401-021-02263-w","article-title":"Distinct amyloid-\u03b2 and tau-associated microglia profiles in Alzheimer\u2019s disease","volume":"141","author":"Gerrits","year":"2021","journal-title":"Acta Neuropathol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1016\/S0140-6736(24)01883-X","article-title":"Passive anti-amyloid \u03b2 immunotherapy in Alzheimer\u2019s disease-opportunities and challenges","volume":"404","author":"Heneka","year":"2024","journal-title":"Lancet"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s40035-025-00465-w","article-title":"Second-generation anti-amyloid monoclonal antibodies for Alzheimer\u2019s disease: Current landscape and future perspectives","volume":"14","author":"Kim","year":"2025","journal-title":"Transl. Neurodegener."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e20200785","DOI":"10.1084\/jem.20200785","article-title":"Anti-human TREM2 induces microglia proliferation and reduces pathology in an Alzheimer\u2019s disease model","volume":"217","author":"Wang","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1056\/NEJMoa2203395","article-title":"Trial of cinpanemab in early Parkinson\u2019s disease","volume":"387","author":"Lang","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1056\/NEJMoa2202867","article-title":"Trial of prasinezumab in early-stage Parkinson\u2019s disease","volume":"387","author":"Pagano","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e1801362","DOI":"10.1002\/adma.201801362","article-title":"Overcoming the Blood-Brain Barrier: The Role of Nanomaterials in Treating Neurological Diseases","volume":"30","author":"Furtado","year":"2018","journal-title":"Adv. Mater."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1007\/s00604-022-05353-y","article-title":"Graphene quantum dots: Synthesis, properties, and applications to the development of optical and electrochemical sensors for chemical sensing","volume":"189","author":"Nesakumar","year":"2022","journal-title":"Mikrochim. Acta"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5294","DOI":"10.1038\/srep05294","article-title":"Formation mechanism and optimization of highly luminescent N-doped graphene quantum dots","volume":"4","author":"Qu","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1007\/s10311-020-00984-0","article-title":"Green synthesis, biomedical and biotechnological applications of carbon and graphene quantum dots. A review","volume":"18","author":"Iravani","year":"2020","journal-title":"Environ. Chem. Lett."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Rostampour Ghareghozloo, E., Mahdavimehr, M., Meratan, A.A., Nikfarjam, N., Ghasemi, A., Katebi, B., and Nemat-Gorgani, M. (2020). Role of surface oxygen-containing functional groups of graphene oxide quantum dots on amyloid fibrillation of two model proteins. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0244296"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.jes.2018.07.014","article-title":"Cytotoxicity and autophagy induction by graphene quantum dots with different functional groups","volume":"77","author":"Xie","year":"2019","journal-title":"J. Environ. Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"120888","DOI":"10.1016\/j.biomaterials.2021.120888","article-title":"The protein corona hampers the transcytosis of transferrin-modified nanoparticles through blood-brain barrier and attenuates their targeting ability to brain tumor","volume":"274","author":"Xiao","year":"2021","journal-title":"Biomaterials"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2691","DOI":"10.2147\/IJN.S445398","article-title":"Utilization of Nitrogen-Doped Graphene Quantum Dots to Neutralize ROS and Modulate Intracellular Antioxidant Pathways to Improve Dry Eye Disease Therapy","volume":"19","author":"Wu","year":"2024","journal-title":"Int. J. Nanomed."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5760","DOI":"10.1021\/acsabm.9b00784","article-title":"Graphene Quantum Dots Induce Autophagy and Reveal Protection Against Hydrogen Peroxide-Induced Oxidative Stress Injury","volume":"2","author":"Hua","year":"2019","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.toxlet.2022.05.006","article-title":"In vivo toxicity assessment of four types of graphene quantum dots (GQDs) using mRNA sequencing","volume":"363","author":"Deng","year":"2022","journal-title":"Toxicol. Lett."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"102615","DOI":"10.1016\/j.mtbio.2025.102615","article-title":"Material-based neuroimaging and biomarker detection for central nervous system disorder","volume":"35","author":"Yu","year":"2025","journal-title":"Mater. Today Bio"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3425","DOI":"10.1021\/acsbiomaterials.3c00369","article-title":"Cancer Therapeutic siRNA Delivery and Imaging by Nitrogen- and Neodymium-Doped Graphene Quantum Dots","volume":"9","author":"Valimukhametova","year":"2023","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Walton-Raaby, M., Woods, R., and Kalyaanamoorthy, S. (2023). Investigating the Theranostic Potential of Graphene Quantum Dots in Alzheimer\u2019s Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119476"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Mansuriya, B.D., and Altintas, Z. (2020). Applications of Graphene Quantum Dots in Biomedical Sensors. Sensors, 20.","DOI":"10.3390\/s20041072"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Beygisangchin, M., Jakmunee, J., Kungwan, N., Ounnunkad, K., Sangthong, P., Baghdadi, A.H., and Kamarudin, S.K. (2026). Graphene Quantum Dot-Based Biosensors: Recent Advances in Functionalization Strategies and Biomedical Applications. Biosensors, 16.","DOI":"10.3390\/bios16050249"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"120001","DOI":"10.1016\/j.cca.2024.120001","article-title":"Electrochemical biosensors in early detection of Parkinson disease","volume":"565","author":"Khatami","year":"2025","journal-title":"Clin. Chim. Acta"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"115196","DOI":"10.1016\/j.addr.2024.115196","article-title":"Intranasal drug delivery: The interaction between nanoparticles and the nose-to-brain pathway","volume":"207","author":"Chen","year":"2024","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s40035-025-00481-w","article-title":"Nose-to-brain drug delivery: From bench to bedside","volume":"14","author":"Drath","year":"2025","journal-title":"Transl. Neurodegener."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"19450","DOI":"10.1039\/D0NR05003B","article-title":"Graphene oxide sheets and quantum dots inhibit \u03b1-synuclein amyloid formation by different mechanisms","volume":"12","author":"Ghaeidamini","year":"2020","journal-title":"Nanoscale"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1016\/j.ijbiomac.2022.11.175","article-title":"Charge modifications of graphene oxide enhance the inhibitory effect on insulin amyloid fibrillation based on electrostatic interactions","volume":"225","author":"Sun","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"19060","DOI":"10.1039\/C5NR06282A","article-title":"Graphene quantum dots for the inhibition of \u03b2 amyloid aggregation","volume":"7","author":"Liu","year":"2015","journal-title":"Nanoscale"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2662693","DOI":"10.1080\/14686996.2026.2662693","article-title":"Characterization and evaluation of the ability of graphene quantum dots to affect \u03b1-synuclein aggregation in synucleinopathy models","volume":"27","author":"Oz","year":"2026","journal-title":"Sci. Technol. Adv. Mater."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"10736","DOI":"10.1021\/ja5049626","article-title":"Chiral effect at protein\/graphene interface: A bioinspired perspective to understand amyloid formation","volume":"136","author":"Qing","year":"2014","journal-title":"J. Am. Chem. Soc."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"112971","DOI":"10.1016\/j.fct.2022.112971","article-title":"Respiratory exposure to graphene quantum dots causes fibrotic effects on lung, liver and kidney of mice","volume":"163","author":"Wu","year":"2022","journal-title":"Food Chem. Toxicol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.jcis.2024.04.111","article-title":"In silico study on graphene quantum dots modified with various functional groups inhibiting \u03b1-synuclein dimerization","volume":"667","author":"Wu","year":"2024","journal-title":"J. Colloid Interface Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1002\/mds.27511","article-title":"Untangling alpha synuclein fibrils by graphene quantum dots","volume":"33","author":"Ysselstein","year":"2018","journal-title":"Mov. Disord."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"146205","DOI":"10.1016\/j.ijbiomac.2025.146205","article-title":"Targeting amyloid \u03b242 aggregation using a structurally defined graphene quantum dot model: A combined molecular and biological investigation","volume":"321","author":"Shaker","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1021\/acschemneuro.7b00015","article-title":"Fluorine Functionalized Graphene Quantum Dots as Inhibitor against hIAPP Amyloid Aggregation","volume":"8","author":"Yousaf","year":"2017","journal-title":"ACS Chem. Neurosci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1021\/acschemneuro.7b00439","article-title":"Synergistic Inhibitory Effect of GQDs-Tramiprosate Covalent Binding on Amyloid Aggregation","volume":"9","author":"Liu","year":"2018","journal-title":"ACS Chem. Neurosci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"148951","DOI":"10.1016\/j.ijbiomac.2025.148951","article-title":"Comparative anti-amyloidogenic potential of pristine and nitrogen doped graphene quantum dots against amyloid beta protein","volume":"333","author":"Tiwari","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2980","DOI":"10.1038\/s41467-024-47167-x","article-title":"Halogen doped graphene quantum dots modulate TDP-43 phase separation and aggregation in the nucleus","volume":"15","author":"Zhang","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.jcis.2024.05.072","article-title":"Graphene acid quantum dots: A highly active multifunctional carbon nano material that intervene in the trajectory towards neurodegeneration","volume":"670","author":"ElMorsy","year":"2024","journal-title":"J. Colloid Interface Sci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"8692","DOI":"10.1021\/acsnano.4c15283","article-title":"Graphene Quantum Dots Attenuate TDP-43 Proteinopathy in Amyotrophic Lateral Sclerosis","volume":"19","author":"Park","year":"2025","journal-title":"ACS Nano"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"7762","DOI":"10.1039\/C8CC03235A","article-title":"Chiral modulation of amyloid beta fibrillation and cytotoxicity by enantiomeric carbon dots","volume":"54","author":"Malishev","year":"2018","journal-title":"Chem. Commun."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"7378","DOI":"10.1039\/D3TB00850A","article-title":"Blocking tau transmission by biomimetic graphene nanoparticles","volume":"11","author":"Zhu","year":"2023","journal-title":"J. Mater. Chem. B"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2500065","DOI":"10.1002\/anbr.202500065","article-title":"N-Amino Peptide-Graphene Quantum Dot Loaded Small Extracellular Vesicles for Targeted Therapy of Tauopathies","volume":"5","author":"Zhu","year":"2025","journal-title":"Adv. Nanobiomed. Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1021\/acs.nanolett.0c03741","article-title":"Graphene Quantum Dots Alleviate Impaired Functions in Niemann-Pick Disease Type C in Vivo","volume":"21","author":"Kang","year":"2021","journal-title":"Nano Lett."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"4153","DOI":"10.1016\/j.cell.2022.09.033","article-title":"TREM2 drives microglia response to amyloid-\u03b2 via SYK-dependent and -independent pathways","volume":"185","author":"Wang","year":"2022","journal-title":"Cell"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s13024-022-00588-y","article-title":"TREM2 dependent and independent functions of microglia in Alzheimer\u2019s disease","volume":"17","author":"Hou","year":"2022","journal-title":"Mol. Neurodegener."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.neuropharm.2018.11.030","article-title":"Graphene quantum dots inhibit T cell-mediated neuroinflammation in rats","volume":"146","author":"Tosic","year":"2019","journal-title":"Neuropharmacology"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.biomaterials.2017.08.040","article-title":"Graphene quantum dots suppress proinflammatory T cell responses via autophagy-dependent induction of tolerogenic dendritic cells","volume":"146","author":"Spitalsky","year":"2017","journal-title":"Biomaterials"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"12098","DOI":"10.1021\/nn502466z","article-title":"Large graphene quantum dots alleviate immune-mediated liver damage","volume":"8","author":"Volarevic","year":"2014","journal-title":"ACS Nano"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/nature11729","article-title":"NLRP3 is activated in Alzheimer\u2019s disease and contributes to pathology in APP\/PS1 mice","volume":"493","author":"Heneka","year":"2013","journal-title":"Nature"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/s41586-019-1769-z","article-title":"NLRP3 inflammasome activation drives tau pathology","volume":"575","author":"Ising","year":"2019","journal-title":"Nature"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"135279","DOI":"10.1016\/j.neulet.2020.135279","article-title":"Beta-amyloid activates NLRP3 inflammasome via TLR4 in mouse microglia","volume":"736","author":"Liu","year":"2020","journal-title":"Neurosci. Lett."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"7084","DOI":"10.1016\/j.biomaterials.2012.06.060","article-title":"Graphene quantum dots as autophagy-inducing photodynamic agents","volume":"33","author":"Markovic","year":"2012","journal-title":"Biomaterials"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s12989-020-00363-1","article-title":"Induction of ferroptosis in response to graphene quantum dots through mitochondrial oxidative stress in microglia","volume":"17","author":"Wu","year":"2020","journal-title":"Part. Fibre Toxicol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s12989-022-00464-z","article-title":"Nitrogen-doped graphene quantum dots induce ferroptosis through disrupting calcium homeostasis in microglia","volume":"19","author":"Wu","year":"2022","journal-title":"Part. Fibre Toxicol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"10060","DOI":"10.1039\/D5RA07458D","article-title":"High-affinity nitrogen-doped graphene quantum dots for selective in vivo and ex vivo detection of amyloid-\u03b2 plaques in an Alzheimer\u2019s disease rat model","volume":"16","author":"Bahman","year":"2026","journal-title":"RSC Adv."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1039\/D2SC05897A","article-title":"In vivo visualization of enantioselective targeting of amyloid and improvement of cognitive function by clickable chiral metallohelices","volume":"14","author":"Du","year":"2023","journal-title":"Chem. Sci."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"120643","DOI":"10.1016\/j.ecoenv.2026.120643","article-title":"Unmasking aminated graphene quantum dots neurotoxicity in freshwater planarian: Dopaminergic disruption and reversible motor dysfunction at sublethal doses","volume":"323","author":"Gu","year":"2026","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.apmt.2018.11.011","article-title":"Nitrogen and Boron Dual-Doped Graphene Quantum Dots for Near-Infrared Second Window Imaging and Photothermal Therapy","volume":"14","author":"Wang","year":"2019","journal-title":"Appl. Mater. Today"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"100334","DOI":"10.1016\/j.impact.2021.100334","article-title":"Increased lipid peroxidation by graphene quantum dots induces ferroptosis in macrophages","volume":"23","author":"Shao","year":"2021","journal-title":"NanoImpact"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.tox.2014.10.011","article-title":"Graphene quantum dots induce apoptosis, autophagy, and inflammatory response via p38 mitogen-activated protein kinase and nuclear factor-\u03baB mediated signaling pathways in activated THP-1 macrophages","volume":"327","author":"Qin","year":"2015","journal-title":"Toxicology"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"142638","DOI":"10.1016\/j.jhazmat.2026.142638","article-title":"Unveiling the neurotoxic mechanism of amino-functionalized graphene quantum dots: Mitophagy-driven ferroptosis underlies progressive anxiety-like behaviors","volume":"514","author":"Fan","year":"2026","journal-title":"J. Hazard. Mater."}],"container-title":["Nanomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-4991\/16\/18\/1158\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:25:59Z","timestamp":1789619159000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-4991\/16\/18\/1158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":124,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["nano16181158"],"URL":"https:\/\/doi.org\/10.3390\/nano16181158","relation":{},"ISSN":["2079-4991"],"issn-type":[{"value":"2079-4991","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]}}}