Preprint / Version 1

Nanotechnology as New Strategy Against Different Dementia Types: Current State of Art

Authors

  • Nelson Duran Laboratory of Urogenital Carcinogenesis and Immunotherapy, Department of Structural and Functional Biology, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil
  • Wagner J Favaro Laboratory of Urogenital Carcinogenesis and Immunotherapy, Department of Structural and Functional Biology, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil
  • Gerson Nakazato Laboratory of Basic and Applied Bacteriology, Department of Microbiology, Biology Sciences Center, Universidade Estadual de Londrina (UEL), Londrina, PR, Brazil

DOI:

https://doi.org/10.21467/preprints.706

Abstract

Dementia, mainly Alzheimer’s disease (AD), is quite significant worldwide. Several dementia types are expected to affect approximately 140 million people by 2025 due to the global population’s aging process. Accordingly, nanotechnology emerges as promising research field. The most important aim of nanotechnology for nanomedicine and Alzheimer’s therapy lies in developing an efficient medicine, as safe as possible, based on new assertive research substantiated by subsequent clinical studies. The fast upgrades in nanotechnology and nanomedicine observed in the last few years have opened room for achieving an AD therapy. Nanomaterials have characteristic features, such as physical and chemical stability, high surface area: volume ratios, as well as programmable production. Furthermore, it is possible customizing these nanomaterials to turn them into special candidates to be used as both therapeutic agents and nanomedicine carriers. The present review deals with upgrades and challenges posed on the diversity of AD therapy nanomaterials such as carbon nanoparticles, lipidic nanocarriers, lipid functionalized, polymeric and metallic nanoparticles, biotherapeutics (monoclonal antibodies) and clinical nanomedicine applications. It is possible to avoid, delay or stop AD progression based associated efforts in nanomedicine aimed at raising the expectation of millions of patients worldwide.

Keywords:

Dementia, Alzheimer, Immunotherapy

Downloads

Download data is not yet available.

References

Aphios-2021. Safety, Tolerability and Efficacy Assessment of Intranasal Nanoparticles of APH-1105, A Novel Alpha Secretase Modulator For Mild to Moderate Cognitive Impairment Due to Alzheimer’s Disease (AD). clinicaltrials.gov; Report No.: NCT03806478. 2021. Available online: https://clinicaltrials.gov/ct2/show/NCT03806478 (accessed on 28 March 2023).

Arya M, Kumar MKM, Sabitha M, Menon KN, Sreeja C. Nair SC. Nanotechnology approaches for enhanced CNS delivery in treating Alzheimer's disease. J Drug Deliv Sci Technol 2019; 51:297-309. https://doi.org/10.1016/j.jddst.2019.03.022,

AS-2024. AntibodySociety, Antibody therapeutics approved or in regulatory review in the EU or US, (n.d.). 2024; https://www.antibodysociety.org/resources/approved-antibodies/

Austria Jr ES, Akhavan B. Polymeric nanoparticle synthesis for biomedical applications: advancing from wet chemistry methods to dry plasma technologies. Nanoscale 2025; 17: 13020. DOI: 10.1039/d5nr00436e.

Ayub A, Wettig S. An overview of nanotechnologies for drug delivery to the brain. Pharmaceutics 2022; 14: 224. DOI: 10.3390/pharmaceutics14020224

Balaban H, Naz?ro?lu M, Demirci K, Ovey IS. The protective role of selenium on scopolamine-induced memory impairment, oxidative stress, and apoptosis in aged rats: The involvement of TRPM2 and TRPV1 channels. Mol Neurobiol 2017; 54:2852-2868. https://doi.org/10.1007/s12035-016-9835-0.

Banks WA, Rhea EM, Reed MJ, Erickson MA. The penetration of therapeutics across the blood-brain barrier: Classic case studies and clinical implications. Cell Rep Med 2024; 5: 101760., https://doi.org/10.1016/j.xcrm.2024.101760.

Barrera-Ocampo A. Monoclonal antibodies and aptamers: The future therapeutics for Alzheimer’s disease. Acta Pharm Sin B 2024; 14: 2795–2814. https://doi.org/10.1016/j.apsb.2024.03.034.

Bhabad A, Wakade A, Salve M. Brief review on niosome. Int J Pharm Sci 2024; 2: 1668-1673. https://doi.org/10.5281/zenodo.1424555.

Cai J, Li B, Feng G, Zhang J, Fan H, Zheng B. Biomolecular interactions of carbon nanotubes with amyloid-? proteins. J Mater Chem B, 2025; 13: 6664-6678. https://doi.org/10.1039/D5TB00153F.

Cao Y, Zhang R. The application of nanotechnology in treatment of Alzheimer’s disease. Front Bioeng Biotechnol 2022; 10: 1042986. doi: 10.3389/fbioe. 2022.1042986.

Capocefalo A, Deckert-Gaudig T, Brasili F, Postorino P, Deckert V. Unveiling the interaction of protein fibrils with gold nanoparticles by plasmon enhanced nano-spectroscopy. Nanoscale 2021; 13: 14469-14479. https://doi.org/10.1039/ D1NR03190B.

Celardo I, Pedersen JZ, Traversa E, Ghibelli L. Pharmacological potential of cerium oxide nanoparticles. Nanoscale 2011; 3: 1411-1420. https://doi.org/10.1039/C0NR00875C.

Chakroborty S, Nath N, Sahoo S, Singh BP, Bal T, Tiwari K, et al. A review of emerging trends in nanomaterial-driven AI for biomedical applications. Nanoscale Adv 2025; 7: 3619–3630. doi: 10.1039/d5na00032g.

Chakraborty B, Patel G, Padhan B, Das J, Patel M. Evolution of lipid nanoparticles as charioteers of Alzheimer’s disease therapeutics. Appl Mater Today 2024; 41:102442. https://doi.org/10.1016/j.apmt.2024.102442.

Chen L, Lin J, Yi J, Weng Q, Zhou Y, Han Z, et al. A tyrosinase-induced fluorescence immunoassay for detection of tau protein using dopamine-functionalized CuInS2/ZnS quantum dots. Anal Bioanal Chem 2019; 411: 5277?5285. doi: 10.1007/s00216-019-01909-9.

Cheng F, Kotha S, Fu M, Yang Q, Wang H, He W, et al. Nanozyme enabled protective therapy for neurological diseases. Nano Today 2024; 54: 102142. https://doi.org/10.1016/j.nantod.2023.102142.

Cheng G, Xie A, Yan Z, Zhu X, Song Y, Chen T. Nanomedicines for Alzheimer's disease: Therapies based on pathological mechanisms. Brain-X 2023; 1: e27. https://doi.org/10.1002/brx2.27.

Chiang MC, Yang YP, Nicol CJB, Wang CJ. gold nanoparticles in neurological diseases: A review of neuroprotection. Int J Mol Sci 2024; 25: 2360. doi: 10.3390/ijms25042360.

Chung YJ, Kim K, Lee BII, Park CB. Carbon nanodot-sensitized modulation of Alzheimer's ?-amyloid self-assembly, disassembly, and toxicity. Nano Micro Small 2017; 13: 1700983. https://doi.org/10.1002/smll.201700983

Cui D, Kong N, Yang W, Yan F. Recent advances in nano-architectonics of two-dimensional nanomaterials for dental biosensing and drug delivery. Adv Colloid Interface Sci 2025; 337:103388. https://doi.org/10.1016/j.cis.2024.103388.

Cummings J, Zhou Y, Lee G, Zhong K, Fonseca J, Cheng F. Alzheimer’s disease drug development pipeline: 2024. Alzheimers Dement (N Y). 2024; 10: e12465. doi: 10.1002/trc2.12465.

D’Alessandro MCB, Kanaan, S, Geller M, Praticò D, Daher JPL. Mitochondrial dysfunction in Alzheimer’s disease. Ageing Res Rev 2025; 107: 102713. https://doi.org/10.1016/j.arr.2025.102713.4.

Dhariwal R, Jain M, Mir YR, Singh A, Jain B, Kumar P, Tariq M, Verma D, Deshmukh K, Yadav VK and Malik T. Targeted drug delivery in neurodegenerative diseases: the role of nanotechnology. Front Med 2025; 12: 1522223. doi: 10.3389/fmed.2025.1522223.

Durán N, Fávaro WJ, Nakazato, G. Progress in the treatment of Alzheimer’s disease. AIJR preprint. 2025.in press.

Far BF, Safaei M, Pourmolaei A, Adibamini S, Shirdel S, Shirdel S, et al. Exploring curcumin-loaded lipid-based nanomedicine as efficient targeted therapy for Alzheimer’s diseases. ACS Appl Bio Mater 2024; 7: 3535?3555.

FDA-2024. FDA approves treatment for adults with Alzheimer’s disease. FDA, (n.d.). https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatm ent-adults-alzheimers-disease (accessed July 22, 2024).

Fernández-García R, Lalatsa A, Statts L, Bolás-Fernández F, Ballesteros, M. P.; et al. Serrano, D. R. Transferosomes a nanocarriers for drugs across the skin: Quality by design from lab to industrial scale. Int J Pharm 2020; 573: 118817. https://doi.org/10.1016/j.ijpharm.2019.118817.

Gangopadhyay A, Dandagi PM, Sutar KP. development and evaluation of thermoreversible ethosomal gel of donepezil hydrochloride for intranasal delivery. J Pharm Innov 2023; 18: 238?246.

https://doi.org/10.1007/s12247-022-09636-y.

Gao M, Li Y, Ho W, Chen C, Chen Q, Li F, et al. Targeted mRNA nanoparticles ameliorate blood–brain barrier disruption postischemic stroke by modulating microglia polarization, ACS Nano 2024; 18: 3260–3275, https://doi.org/10.1021/acsnano.3c09817.

Georgieva D, Nikolova D, Vassileva E, Kostova B. Chitosan-based nanoparticles for targeted nasal galantamine delivery as a promising tool in Alzheimer’s disease therapy. Pharmaceutics 2023; 15: 829. DOI:10.3390/pharmaceutics15030829

Ghamarsoorat F, Rahbarian R, Arasteh A. Green synthesis of silver nanoparticles using Pimpinella anisum L. seed extract: Synthesis, characterization, and anti-Alzheimer’s activity. Inorg Nano-Metal Chem 2024; 1–11. https://doi.org/10.1080/24701556.2024.2358338.

Gonzalez-Duarte A, Ulloa-Aguirre A. A brief journey through protein misfolding in transthyretin amyloidosis (ATTR amyloidosis). Int J Mol Sci 2021; 22:13158. doi: 10.3390/ijms222313158.

Guo Q, Yang Y, Zhao L, Chen J, Duan GX, Yang ZX, et al., Graphene oxide toxicity in W 1118 flies. Sci Total Environ 2022; 805: 150302. https://doi.org/10.1016/j.scitotenv.2021.150302

Gupta J, Fatima MT, Islam Z, Khan RH, Uversky VN, Salahuddin P. Nanoparticle formulations in the diagnosis and therapy of Alzheimer's disease. Inter J Biol Macromol 2019;130: 515-526. https://doi.org/ 10.1016/j.ijbiomac.2019.02.156.

Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG. Cancer drug resistance: an evolving paradigm. Nat Rev Cancer 2013; 13: 714–726, https:// doi.org/10.1038/nrc3599.

Hong Q, Jin X, Zhou C, Shao J. Gold nanoparticles with amyloid-? reduce neurocell cytotoxicity for the treatment and care of Alzheimer’s disease therapy. Gold Bull 2023; 56: 135–144. https://doi.org/10.1007/s13404-023-00327-1

Hosny S, Mohamed LZ, Ragab MS, Alomoush QK, Abdalla EM, Aly SA . Nanomaterials in biomedical applications: opportunities and challenges—a review. Chem Pap 2025; 79: 2657–2678. https://doi.org/10.1007/s11696-025-03937-5.

Hu Y, Guo H, Cheng S, Sun J, Du J, Liu X, et al. Functionalized Cerium Dioxide Nanoparticles with Antioxidative Neuroprotection for Alzheimer's Disease. Int J Nanomed 2023a;18: 6797-6812. doi: 10.2147/IJN.S434873.

Hu L, Tao Y, Jiang Y, Qin F. Recent progress of nanomedicine in the treatment of Alzheimer’s disease. Front. Cell Dev. Biol. 2023b; 11:1228679. doi: 10.3389/fcell.2023.1228679.

Ikram H. Nanomedicine: Transforming neurological therapies and precision medicine. J Neurol Neuromedicine 2025; 9: 1-4. doi:

29245/2572.942X

Iyer M, Elangovan A, Sennimalai R, Babu HWS, Thiruvenkataswamy S, Krishnan J, et al. Chitosan – An alternative drug delivery approach for neurodegenerative diseases. Carbohydr Polym Technol Appl 2024; 7: 100460. https://doi.org/10.1016/j.carpta.2024.100460.

Jin YB, Sun YX, Chen YJ, Lei JT, Wei GH. Molecular dynamics simulations reveal the mechanism of graphene oxide nanosheet inhibition of A? peptide aggregation. Phys Chem Chem Phys 2019; 21: 10981?10991. https://doi.org/10.1039/C9CP01803D.

Jojo GM, Kuppusamy G, De A, Reddy-Karri VVSN. Formulation and optimization of intranasal nanolipid carriers of pioglitazone for the repurposing in Alzheimer’s disease using Box-Behnken design. Drug Dev Ind Pharm 2019; 45: 1061–1072. doi: 10.1080/03639045.2019.1593439.

Jokar S, Khazaei S, Gameshgoli XE, Khafaji M, Yarani B, Sharifzadeh M, et al. Amyloid ?-Targeted Inhibitory Peptides for Alzheimer’s Disease: Current State and Future Perspectives. In: Alzheimer’s Disease: Drug Discovery [Internet]. (Huang X, editor) Brisbane (AU): Exon Publications; 2020; Chapter 3: 51-68. PMID: 33400460. doi:10.36255/exonpublications. alzheimersdisease.2020.ch3.

Kadolkar R, Ogale S, Nagesh C. A Review on ethosomes: A promising transdermal approach of drug delivery. Int J Pharm Sci 2025; 3: 2398-2406. doi:10.5281/zenodo.14762118.

Karran E, De Strooper B. The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics. Nat Rev Drug Discov. 2022; 21:306-318. https://doi.org/10.1038/s41573-022-00391-w.

Katari O, Yadav S, Akhtar J, Jain S. Micelles-based drug delivery for dementia. Editor(s): Gupta U, Kesharwani P. In Nanomedicine-Based Approaches for the Treatment of Dementia, Academic Press, 2023; 8: 169-192. https://doi.org/10.1016/B978-0-12-824331-2.00002-9.

Kodiyala G. Meenugula K, Rao KY, Nadimikeri J, Chapati VP, Salkapuram S, et al. Phyto-mediated synthesis of silver nanoparticles using Erythrina variegata L. leaf extract and evaluation of their anti-bacterial, anti-Alzheimer, antioxidant and cytotoxic activities. Next Nanotechnology 2025; 7: 100157. https://doi.org/10.1016/j.nxnano.2025.100157.

Kulkarni P, Rawtani D, Barot T. Design, development, and in-vitro/in-vivo evaluation of intranasally delivered rivastigmine and n-acetyl cysteine loaded bifunctional niosomes for applications in combinative treatment of Alzheimer’s disease. Eur J Pharm Biopharm 2021; 163: 1?15. https://doi.org/10.1016/j.ejpb.2021.02.015.

Kumar K, Annasamy G, Rekulapally PSNS, Krishnan S. Nanotechnology interventions in neuroscience: Current perspectives and strategies. In Applications of nanotechnology in drug discovery and delivery (Egbuna C, G?man M-A, Jeevanandam J. Eds.) Amsterdam, Netherlands: Elsevier), 2022; 11; 255–289. https://doi.org/10.1016/B978-0-12-824408-1.00015-6.

Kurul F, Turkmen H, Cetin AE, Topkaya SN. Nanomedicine: How nanomaterials are transforming drug delivery, bio-imaging, and diagnosis. Next Nanotechnology 2025; 7: 100129. https://doi.org/10.1016/j.nxnano.2024.100129.

Kwon HJ, Cha MY, Kim D, Kim DK, Soh M, Shin K, et al. Mitochondria-targeting ceria nano particles as antioxidants for Alzheimer’s disease. ACS Nano 2016; 10: 2860?2870. https://doi.org/10.1021/acsnano.5b08045.

La Barbera L, Mauri E, D’Amelio M, Gori M. Functionalization strategies of polymeric nanoparticles for drug delivery in Alzheimer’s disease: Current trends future Perspective. Front Neurosci 2022; 16: 939855. doi: 10.3389/fnins.2022.939855.

Laib I, Gheraissa N, Benaissa A, Benkhira L, Azzi M, Benaissa Y, et al. Tailoring innovative silver nanoparticles for modern medicine: The importance of size and shape control and functional modifications. Mat Today Bio 2025;102071. https://doi.org/10.1016/j.mtbio.2025.102071.

Li D, Wang X, Wang S, Song X, Fang L, Zhang Y, et al. Multifunctional carbon dots inhibit the amyloid fibrillation and scavenge free radicals. J Mol Struct 2025a; 1326:141134. https://doi.org/10.1016/j.molstruc.2024.141134.

Li N, Zhang Z, Shen L, Song G, Tian J, Liu Q, et al. Selenium metabolism and selenoproteins function in brain and encephalopathy. Sci China Life Sci 2025b; 68: 628–656. https://doi.org/10.1007/s11427-023-2621-7.

Li P, Yuan W, Hu K. Porous CeO2 nanozyme with visible-light-enhanced catalase-mimicking activities by ligand-to-metal charge transfer. iScience 2025c; 28: 112149. https://doi.org/10.1016/j.isci.2025.112149.

Li L, He RD, Yan HL, Leng ZW, Zhu S, Gu ZJ. Nanotechnology for the diagnosis and treatment of Alzheimer’s disease: A bibliometric analysis. Nano Today 2022; 47: 101654. https://doi.org/10.1016/j.nantod.2022.101654.

Liao YH, Chang YJ, Yoshiike Y, Chang YC, Chen YR. Negatively charged gold nanoparticles inhibit Alzheimer’s amyloid ? fibrillization, induce fibril dissociation, and mitigate neuro toxicity. Small 2012; 8: 3631?3639. doi: 10.1002/smll.201201068.

Lim JL, Lin CJ, Huang CC, Chang LC. Curcumin derived carbon quantum dots: Dual actions in mitigating tau hyperphosphorylation and amyloid beta aggregation. Colloids Surf B 2024; 234: 113676. https://doi.org/10.1016/j.colsurfb.2023.113676.

Lin C, Huang X, Xue Y, Jiang S, Chen C, Liu Y et al., Advances in medical devices using nanomaterials and nanotechnology: Innovation and regulatory science. Bioactive Mat 2025; 48: 353-369. https://doi.org/10.1016/ j.bioactmat.2025.02.017.

Liu PX, Zhang TY, Chen QJ, Li C, Chu YC, Guo Q, et al. Biomimetic dendrimer-peptide conjugates for early multi-target therapy of Alzheimer’s disease by inflammatory microenvironment modulation. Adv. Mater 2021; 33: 2100746. doi: 10.1002/adma.202100746.

Liu L, He H, Du B, He Y. Nanoscale drug formulations for the treatment of Alzheimer's disease progression. RSC Adv 2025; 15: 4031-4078. doi: 10.1039/D4RA08128E .

Lotfy A, AboQuella NM, Wang H. Mesenchymal stromal/stem cell (MSC)-derived exosomes in clinical trials. Stem Cell Res Ther 2023; 14: 66 https://doi.org/10.1186/s13287-023-03287-7.

Lowe TL, Strzelec A, Kiessling LL, Murphy RM. Structure-function relationships for inhibitors of beta-amyloid toxicity containing the recognition sequence KLVFF. Biochemistry. 2001; 40:7882-7889. https://doi.org/10.1021/bi002734u

Malek SZ, Arasteh A. In vitro regulation of amyloid production in Alzheimer’s disease via curcumin-loaded silver nanoparticles with antioxidant and acetylcholinesterase-inhibiting properties. Mol Neurobiol 2025; In press. https://doi.org/10.1007/s12035-025-05125-8.

Malishev R, Arad E, Bhunia SK, Shaham-Niv S, Kolusheva S, Gazit E, et al. Chiral modulation of amyloid beta fibrillation and cytotoxicity by enantiomeric carbon dots. Chem Commun 2018; 54: 7762?7765. doi: 10.1039/c8cc03235a.

Medesispharma-2022. Available online: https://www.medesispharma.com/clinical-stage-products/drug-to-treat-neurodegenerative-diseases/ (accessed on 9 December 2022).

Mejias S, Sneed KB, Pathak Y. Recent trends in nano-drug delivery systems in the treatment for Alzheimer’s disease. Nano Tech Appl 2025; 8: 1-8. ISSN 2639-9466.

Moghassemi S, Hadjizadeh A. Nano-niosomes as nanoscale drug delivery systems: An illustrated review. J Control Release 2014; 185: 22?36. https://doi.org/10.1016/j.jconrel.2014.04.015.

Monroy Ramirez HC, Salto Sevilla J, Arceo Orozco S, Caloca Camarena F, Flores Peña R, Lopez Mena E, et al. Cerium oxide nanoparticles: a promising nanotherapy approach for chronic degenerative diseases. J Mater Sci: Mater Eng 2025; 20: 69. https://doi.org/10.1186/s40712 025 00295 8.

Mroziak M, Koz?owski G, Ko?odziejczyk W, Pszczo?owska M, Walczak K, Besz?ej JA, et al. Dendrimers—Novel therapeutic approaches for Alzheimer’s disease. Biomedicines 2024; 12: 1899. https://doi.org/10.3390/ biomedicines12081899.

Mullard A. FDA approves third anti-amyloid antibody for Alzheimer disease. Nat Rev Drug Discov 2024; 23: 571.

Naqvi S, Panghal A, Flora SJS. Nanotechnology: A promising approach for delivery of neuroprotective drugs. Front Neurosci 2020; 14: 494. doi: 10.1038/d41573-024-00116-1.

Neely A, Perry C, Varisli B, Singh AK, Arbneshi T, Senapati D, et al. Ultrasensitive and highly selective detection of Alzheimer's disease biomarker using two-photon Rayleigh scattering properties of gold nanoparticle. ACS Nano 2009; 3: 2834-2840. doi: 10.1021/nn900813b

Opatha SAT, Titapiwatanakun V, Chutoprapat R. Transfersomes: A promising nanoencapsulation technique for transdermal drug delivery. Pharmaceutics 2020; 12: 855. https://doi.org/10.3390/pharmaceutics12090855.

Pandya BD, Panchal PK. Niosomes as versatile nanocarriers: from design to therapeutic applications. Eur J Pharm Med Res 2025; 12: 160-170. ISSN 2394-3211 EJPMR.

Pechnikova NA, Domvri K, Porpodis K, Istomina MS, Iaremenko AV, Yaremenko AV. Carbon quantum dots in biomedical applications: advances, challenges, and future prospects. Aggregate 2025; 6: e707. https://doi.org/10.1002/agt2.707.

Peeriga R, Manubolu K. Effect of renal and hepatic diseases on pharmacokinetics. In: Manubolu, K., Peeriga, R., Chandrasekhar, K.B. (eds) A short guide to clinical pharmacokinetics. Springer, Singapore. 2024; 2024:67-95. https://doi.org/10.1007/978-981-97-4283-7_5.

Plissonneau M, Pansieri J, Heinrich-Balard L, Morfin J-F, Stransky-Heilkron N, Rivory P, et al. Gd-nanoparticles functionalization with specific peptides for ß-amyloid plaques targeting. J Nanobiotechnol 2016; 14: 60. https://doi.org/ 10.1186/s12951-016-0212-y.

Pineiro-Alonso L, Rubio-Prego I, Lobyntseva A, Gonzalez-Freire E, Langer R, Alonso MJ. Nanomedicine for targeting brain neurodegeneration: Critical barriers and circadian rhythm considerations. Advan Drug Delivery Rev 2025; 222: 115606. https://doi.org/10.1016/j.addr.2025.115606.

Randhawa S, Saini TC, Bathla M, Bhardwaj R, Dhiman R, Acharya A. Nanomaterials in targeting amyloid-? oligomers: current advances and future directions for Alzheimer's disease diagnosis and therapy. Beilstein J Nanotechnol 2025; 16: 561–580. https://doi.org/10.3762/bjnano.16.44.

Ren CX, Li DD, Zhou QX, Hu XG. Mitochondria targeted TPP-MoS 2 with dual enzyme activity provides efficient neuroprotection through M1/M2 microglial polarization in an Alzheimer’s disease model. Biomaterials 2020; 232: 119752. https://doi.org/10.1016/j.biomaterials.2019.119752.

Ray AS, Ghann WE, Tsoi PS, Szychowski B, Dockery LT, Pak YJ, et al. Set of highly stable amine- and carboxylate-terminated dendronized Au nanoparticles with dense coating and nontoxic mixed-dendronized form. Langmuir 2019; 35: 9, 3391–3403. https://doi.org/10.1021/ acs.langmuir.8b03196.

Saharan R, Paliwal SK, Tiwari A, Tiwari V, Singh R, Beniwal, et al. Exploring graphene and its potential in delivery of drugs and biomolecules. J. Drug Deliv Sci Technol 2023; 84: 104446. https://doi.org/10.1016/j.jddst.2023.104446.

Saleh SR, Abd-Elmegied A, Aly Madhy S, Khattab SN, Sheta E, Elnozahy FY, et al. Brain-targeted Tet-1 peptide-PLGA nanoparticles for berberine delivery against STZ-induced Alzheimer’s disease in a rat model: Alleviation of hippocampal synaptic dysfunction, Tau pathology, and amyloidogenesis. Int J Pharm 2024; 658: 124218. doi: 10.1016/j.ijpharm.2024.124218.

Salem HF, Aboud HM, Abdellatif MM, Abou-Taleb HA. Nose-to-brain targeted delivery of donepezil hydrochloride via novel hyaluronic acid-doped nano transfersomes for Alzheimer’s disease mitigation. J Pharm Sci 2024; 113: 1934?1945. https://doi.org/10.1016/j.xphs.2024.02.014.

Sancey L, Kotb S, Truillet C, Appaix F, Marais A, Elo?se Thomas E, et al. Long-term in vivo clearance of gadolinium-based AGuIX nanoparticles and their biocompatibility after systemic injection. ACS Nano. 2015; 9: 2477-2788. doi 10.1021/acsnano.5b00552.

Scarpa E, Cascione MF, Griego A, Pellegrino P, Moschetti G, De Matteis V. Gold and silver nanoparticles in Alzheimer's and Parkinson's diagnostics and treatments. Ibrain 2023; 9: 298–315. DOI: 10.1002/ibra.12126.

Schroeder V, Savagatrup S, He M, Lin SB, Swager TM. Carbon nanotube chemical sensors. Chem Rev 2019; 119: 599?663. https://doi.org/10.1021/acs.chemrev.8b00340.

Shah RM, Jadhav SR, Bryant G, Kaur IP, Harding IH. On the formation and stability mechanisms of diverse lipid-based nanostructures for drug delivery. Adv Colloid Interface Sci 2025; 338:103402. https://doi.org/10.1016/j.cis.2025.103402.

Sharma A, Rudrawar S, Bharated SB, Jadhav HR. Recent advancements in the therapeutic approaches for Alzheimer's disease treatment: Current and future perspective. RSC Med Chem 2025;16: 652-693. doi: 10.1039/d4md00630e.

Shivananjegowda MG, Hani U, Osmani RAM, Alamri AH, Ghazwani M, Alhamhoom Y, et al. Development and evaluation of solid lipid nanoparticles for the clearance of A? in Alzheimer’s disease. Pharmaceutics 2023; 15: 221. doi: 10.3390/pharmaceutics15010221.

Skalny, A.V., Aschner, M., Santamaria, A, Filippini T, Gritsenko VA, Tizabi Y, et al. The role of gut microbiota in the neuroprotective effects of selenium in Alzheimer’s disease. Mol Neurobiol 2025; 62: 1675–1692. https://doi.org/10.1007/s12035-024-04343-w .

Soliman MG, Davies HA, Sharkey J, Levy R, Madine J. Development of amyloid beta gold nanorod aggregates as optoacoustic probes. PLoS ONE 2022; 17: e0259608. https://doi.org/ 10.1371/journal.pone.0259608.

Soghrati M, Najmi F, Hosseini SS, Yadavi S, Younesi F, Bagheri S, et al., The potential of nanotechnology in treating Alzheimer: A critical review. Series Med Sci 2024; 5:1-19. seriesscience.com .

Song G, Shui R, Wang D, Fang R, Yuan T, Li L, et al. Aptamer-conjugated graphene oxide-based surface assisted laser desorption ionization mass spectrometry for selective extraction and detection of A?1-42 in an Alzheimer’s disease SH-SY5 cell model. Front Aging Neurosci 2022; 14:993281. doi: 10.3389/fnagi.2022.993281.

Song QT, Li JY, Li T, Li HW. Nanomaterials that aid in the diagnosis and treatment of Alzheimer’s disease, resolving blood-brain barrier crossing ability. Adv Sci 2024; 11: 2403473. https://doi.org/10.1002/advs.202403473.

Strojny-Cie?lak B, Pruchniewski M, Sosnowska M, Szczepaniak J, Wierzbicki M. Toxicological insights into graphene family materials: Cytochrome P450 modulation and cellular stress in liver cells. Sci Total Environ 2025; 974:179211. https://doi.org/10.1016/j.scitotenv.2025.179211.

Su D, Chen Z, An X, Yang J, Yang J, Wang X, et al. MicroRNA-195 liposomes for therapy of Alzheimer’s disease. J Control Release 2024; 365: 583?601. doi: 10.1016/j.jconrel.2023.12.003.

Tapia-Arellano A, Cabrera P, Cortés-Adasme E. Riveros A, Hassan N, Kogan MJ. Tau- and ?-synuclein-targeted gold nanoparticles: applications, opportunities, and future outlooks in the diagnosis and therapy of neurodegenerative diseases. J Nanobiotechnol 2024; 22: 248. https://doi.org/ 10.1186/s12951-024-02526-0.

Teixeira MI, Lopes CM, Amaral MH, Costa PC. Chapter 10 - Silver nanoparticles for the management of neurological diseases, Editor(s): Prashant Kesharwani, Silver Nanoparticles for Drug Delivery, Academic Press, 2024; 10: 209-239. https://doi.org/10.1016/B978-0-443-15343-3.00002-4.

Tenchov R, Bird R, Curtze AE, Zhou QQ. Lipid nanoparticles-from liposomes to mRNA vaccine delivery, a landscape of research diversity and advancement. ACS Nano 2021; 15: 16982?17015. https://doi.org/10.1021/acsnano.1c04996.

Thakur G, Micic M, Yang Y, Li W, Movia D, Giordani S, et al. Conjugated quantum dots inhibit the amyloid ? (1?42) fibrillation process. Int J. Alzheimers Dis 2011, 2011, 502386. doi: 10.4061/2011/502386.

Tishkevich DI, Vorobjova AI, Outkina EA, Razanau IU, Zubar TI, Rotkovich AA, et al. Fabrication of high-density vertical CNT arrays using thin porous alumina template for biosensing applications. RSC Adv 2025; 15: 1375. DOI: 10.1039/d4ra06442a.

Tufail S, Sherwani MA, Shamim Z, Abdullah, Goh KW, Alomary MN, et al 2D nanostructures: Potential in diagnosis and treatment of Alzheimer’s disease. Biomed Pharm 2024;170: 116070. https://doi.org/ 10.1016/j.biopha.2023.116070.

van Dyck C H, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, et al. Lecanemab in early Alzheimer’s disease. N Engl J Med 2023; 388: 9?21. doi: 10.1056/NEJMoa2212948.

Varlamova EG, Turovsky EA, Blinova EV. Therapeutic potential and main methods of obtaining selenium nanoparticles. Int J Mol Sci 2021; 22: 10808. https://doi.org/10.3390/ijms221910808.

Villalva MD, Agarwal V, Ulanova M, Sachdev PS, Braidy, N. Quantum dots as a theranostic approach in Alzheimer’s disease: a systematic review. Nanomedicine 2021; 16: 1595? 1611. doi: 10.2217/nnm-2021-0104.

Vijayan A, Sivamaruthi BS, Kesika P, Sisubalan N, Chaiyasut C. Nanoparticle-mediated therapy for Alzheimer’s disease. In: Sivamaruthi, B.S., Sisubalan, N., Kesika, P., Varaprasad, K. (eds) Nanoparticles in modern neurological treatment. nanotechnology in the life sciences. Springer, Cham. 2025; pp 203–223, https://doi.org/10.1007/978-3-031-80185-3_7

Vucic S, Menon P, Huynh W, Mahoney C, HoK S, Hartford A, et al. Efficacy and safety of CNM-Au8 in amyotrophic lateral sclerosis (RESCUE-ALS study): A phase 2, randomised, double-blind, placebo-controlled trial and open label extension. eClinicalMedicine 2023; 60: 102036. doi: 10.1016/j.eclinm. 2023.102036.

Wang K, Yang R, Li J, Wang H, Wan L, He J. Nanocarrier-based targeted drug delivery for Alzheimer’s disease: addressing neuroinflammation and enhancing clinical translation. Front Pharmacol 2025; 16:1591438. doi: 10.3389/fphar.2025.1591438.

Wang WJ, Liu MM, Gao WQ, Sun Y, Dong XY. Co-assembled chitosan-hyaluronic acid nanoparticles as a theranostic agent targeting Alzheimer’s ?-amyloid. ACS Appl Mater Interfaces 2021; 13: 55879?55889. https://doi.org/10.1021/acsami.1c17267.

Wang Z, Wang Y, Li W, Mao F, Sun Y, Huang L, et al. Design, synthesis, and evaluation of multitarget-directed selenium-containing clioquinol derivatives for the treatment of Alzheimer's disease. ACS Chem Neurosci 2014; 5:952-962. doi:10.1021/cn500119g.

Wen MM, El-Salamouni NS, El-Refaie WM, Hazzah HA, Ali MM, Tosi G, et al. Nanotechnology-based drug delivery systems for Alzheimer's disease management: Technical, industrial, and clinical challenges. J Control Release. 2017; 245:95-107. https://doi.org/10.1016/j.jconrel.2016.11.025.

Wilson EN, do Carmo S, Iulita MF, Hall H, Ducatenzeiler A, Marks AR, et al. BACE1 inhibition by microdose lithium formulation NP03 rescues memory loss and early-stage amyloid neuropathology. Transl Psychiatry 2017; 7: e1190. doi: 10.1038/tp.2017.169.

Wilson EN, do Carmo S, Iulita MF, Hall H, Austin GL, Jia DT, et al. Microdose lithium NPo3 diminishes pre-plaque oxidative damage and neuroinflammation in a rat model of Alzheimer’s-like amyloidosis. Curr Alzheimer Res 2018; 15: 1220–1230. doi: 10.2174/1567205015666180904154446.

Wilson EN, do Carmo S, Welikovitch LA, Hall H, Aguilar IF, Foret MK, et al. NPO3, a microdose lithium formulation, blunts early amyloid post-plaque neuropathology in McGill-R-Thy1-APP alzheimer-like transgenic rats. J Alzheimer’s Dis 2020; 73: 723–739. doi: 10.3233/JAD-190862.

Xiao L, Zhao D, Chan WH, Choi MM, Li HW. Inhibition of beta 1?40 amyloid fibrillation with n-acetyl-l-cysteine capped quantum dots. Biomaterials 2010; 31: 91?98. https://doi.org/10.1016/j.biomaterials.2009.09.014.

Xu ST, Yang P, Qian K, Li YX, Guo Q, Wang PZ, et al. Modulating autophagic flux via ROS-responsive targeted micelles to restore neuronal proteostasis in Alzheimer’s disease. Bioact Mater 2022; 11: 300?316. https://doi.org/10.1016/j.bioactmat.2021.09.017.

Yan C, Shao X, Wang Y, Tang S, Li S, Wang C, et al. Application of carbon dots-based nanomaterials in amyloid aggregation disease. Carbon 2025; 234: 119971. https://doi.org/10.1016/j.carbon.2024.119971.

Yan C, Wang C, Shao X, Shu Q, Hu X, Guan P, et al. Dual-targeted carbon-dot-drugs nanoassemblies for modulating Alzheimer’s related amyloid-? aggregation and inhibiting fungal infection. Mater Today Bio 2021; 12: 100167. https://doi.org/10.1016/j.mtbio.2021.100167,

Yang P. Huang QQ, Zhang JH, Li YW, Gao HL, Gu ZP. Natural polyphenolic nanodots for Alzheimer’s disease treatment. Adv Mater 2024b; 36: 2308393. https://doi.org/10.1002/adma.202308393.

Yang H, Tan H, Wen H, Xin P, Liu Y, Deng Z. et al. Recent progress in nanomedicine for the diagnosis and treatment of Alzheimer’s diseases. ACS Nano 2024a; 18: 33792?33826. https://doi.org/10.1021/acsnano.4c11966.

Yanikoglu R, Karakas CY, Ciftci F, Insel MA, Karavelioglu Z, Varol R, et al. Development of graphene oxide-based anticancer drug combination functionalized with folic acid as nanocarrier for targeted delivery of methotrexate. Pharmaceutics 2024; 16: 837. https://doi.org/10.3390/pharmaceutics16060837.

Ye CH, Cheng M, Ma L, Zhang TZ, Sun ZH, Yu CS, et al. Oxytocin nanogels inhibit innate inflammatory response for early intervention in Alzheimer’s disease. ACS Appl Mater Interfaces 2022; 14: 21822?21835. doi: 10.1021/acsami.2c00007.

Yi LX, Tan EK, Zhou ZD. Passive immunotherapy for Alzheimer’s disease: challenges & future directions, J Transl Med 2024; 22: 430. https://doi.org/10.1186/s12967-024-05248-x.

Yin XH, Zhou H, Cao TT, Yang XE, Meng F, Dai X, et al. Rational design of dual-functionalized Gd@C82 nanoparticles to relieve neuronal cytotoxicity in Alzheimer’s disease via inhibition of A? aggregation. ACS Nano 2024; 18: 15416?15431. https://doi.org/10.1021/acsnano.3c08823.

Yin X, Zhou H, Zhang M, Su J, Wang X, Li S, et al. C3N nanodots inhibits A? peptides aggregation pathogenic path in Alzheimer’s disease. Nat Commun 2023; 14: 5718. https://doi.org/10.1038/s41467-023-41489-y.

Zagórska A, Czopek A, Fryc M, Jaromin A, Boyd BJ. Drug discovery and development targeting dementia. Pharmaceuticals 2023; 16: 151. doi:10.3390/ph16020151.

Zhang W, Smith N, Zhou Y, McGee CM, Bartoli M, Fu S, et al., Carbon dots as dual inhibitors of tau and amyloid-beta aggregation for the treatment of Alzheimer's disease. Acta Biomaterialia 2024a; 183: 341-355. https://doi.org/10.1016/j.actbio.2024.06.001.

Zhang WS, Mehta A, Tong ZQ, Esser L, Voelcker NH. Development of polymeric nanoparticles for blood-brain barrier transfer-strategies and challenges. Adv Sci 2021; 8: 2003937. doi: 10.1002/advs.202003937.

Zhang Z, Lu Y, Zhao Y, Cui L, Xu C, Wu, S. Current Developments in chitosan-based hydrogels for water and wastewater treatment: A comprehensive review. ChemistrySelect 2025; 10: e202404061. https://doi.org/10.1002/slct.202404061.

Zhang JF, Zhang YL, Wang JX, Xia YL, Zhang JX, Chen L. Recent advances in Alzheimer’s disease: mechanisms, clinical trials, and new drug development strategies. Signal Transduct Target Ther 2024b; 9: 211. doi: 10.1038/s41392-024-01911-3.

Zhang J, Zhou X, Yu Q, Yang L, Sun D, Zhou Y, et al. Epigallocatechin-3-gallate (EGCG)-stabilized selenium nanoparticles coated with Tet-1 peptide to reduce amyloid-? aggregation and cytotoxicity. ACS Appl Mater Interfaces. 2014; 6: 8475-8487. https://doi.org/10.1021/am501341u.

Zhao Z, Nelson AR, Betsholtz C, et al. Establishment and dysfunction of the blood-brain barrier. Cell 2015; 163:1064-1078. doi: 10.1016/j.cell.2015.10.067.

Zhou H, Yin X, Zhang G, Yang Z, Zhou R. Advancing nanomaterial-based strategies for Alzheimer’s disease: A perspective. JACSAu 2025; 5:1519?1537. http://doi.org/10.1021/jacsau.5c00002.

Downloads

Posted

2025-08-24

Section

Preprints

Categories