Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

Targeted quantum dots: A novel approach for diagnosis and treatment of neurodegenerative diseases

Articles in Press

Document Type : Review Article

Authors
Kiarash Jahazi 1, 2
Leila Etemad 3
Somayeh Marouzi 4
Maryam Hashemi 4, 5
1 School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
2 Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
3 Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
4 Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
5 Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
10.22038/ijbms.2026.94096.20278
Abstract
Nanotechnology-based approaches using quantum dots (QDs) are attracting growing attention for neurodegenerative diseases. These include carbon- and graphene-based nanostructures, ZnO QDs, and emerging black phosphorus nanomaterials, all of which serve as multifunctional theranostic platforms. QDs possess unique properties derived from their crystalline inorganic lattice structures, strong ionic/covalent bonding, optical features, and tunable surfaces. These attributes enhance their applicability in drug delivery, molecular imaging, and biosensors. Furthermore, the ability of QDs to cross the blood-brain barrier (BBB) via receptor-mediated, adsorptive, or carrier-assisted pathways has driven the development of advanced surface functionalization strategies to improve targeting specificity and biocompatibility. This review focuses on the application of targeted QDs in major neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS), highlighting recent preclinical advances, diagnostic and therapeutic mechanisms, and BBB transport strategies. Despite these advances, challenges such as long-term toxicity, biological stability, regulatory approval, and scalable synthesis must be addressed to realize the clinical potential of QD-based nanomedicine in neuroscience fully.
Keywords
Alzheimer&rsquo
s disease (AD)
Neurodegenerative
Parkinson&rsquo
s disease (PD)
Target
QDs (QDs)
Theragnostic
Subjects
1. ElMorsy SM, Gutierrez DA, Valdez S, Kumar J, Aguilera RJ, Noufal M, et al. Graphene acid quantum dots: A highly active multifunctional carbon nano material that intervene in the trajectory towards neurodegeneration. J Colloid Interface Sci 2024; 670: 357-363.
2. Lin X, Galaqin N, Tainaka R, Shimamori K, Kuragano M, Noguchi TQ, et al. Real-time 3D imaging and inhibition analysis of various amyloid aggregations using quantum dots. Int J Mol Sci 2020; 21: 1978.
3. He Z, Yang Q, Li X, Wang Z, Wen S, Dong MJ, et al. Vanadium carbide quantum dots exert efficient anti‐inflammatory effects in lipopolysaccharide‐induced BV2 microglia and mice. Small Sci 2024; 4: 2300334.
4. Imamura Y, Okuzumi A, Yoshinaga S, Hiyama A, Furukawa Y, Miyasaka T, et al. Quantum-dot-labeled synuclein seed assay identifies drugs modulating the experimental prion-like transmission. Commun Biol 2022; 5: 636.
5. Ye P, Li L, Qi X, Chi M, Liu J, Xie M. Macrophage membrane-encapsulated nitrogen-doped carbon quantum dot nanosystem for targeted treatment of Alzheimer’s disease: Regulating metal ion homeostasis and photothermal removal of β-amyloid. J Colloid Interface Sci 2023; 650: 1749-1761.
6.Tosat-Bitrián C, Bueso de Barrio JA, Stewart MH, Susumu K, Medintz IL, Díaz SA, et al. Membrane-targeted quantum dot-based BACE1 activity sensors for in vitro and in cellulo assays. ACS Appl Mater Interfaces 2024; 16: 63186-63194.
7. Yang J, Hu D, Xing P, Zhang Y, Ye Z, Liu K, et al. Machine learning framework for multi-endpoint quantum dot toxicity prediction with organoid validation and drug target discovery. Toxics 2025; 13: 967-971.
8. Raut J, Sherpa RD, Jana SK, Mandal SM, Mandal S, Hui SP, et al. In vivo monitoring of GABA by N-Doped carbon quantum dots. ACS Appl Nano Mater 2024; 7: 23278-23287.
9. Kaliyaperumal P, Renganathan S, Arumugam K, Aremu BR. Engineered graphene quantum dot nanocomposite triggers α-synuclein defibrillation: Therapeutics against Parkinson’s disease. Nanomedicine 2023; 47: 102608.
10. Wu T, He K, Ang S, Ying J, Zhang S, Zhang T, et al. Impairments of spatial learning and memory following intrahippocampal injection in rats of 3-mercaptopropionic acid-modified CdTe quantum dots and molecular mechanisms. Int J Nanomedicine 2016; 11: 2737-2755.
11. Kaliyaperumal P, Renganathan S, Arumugam K, Aremu BR. Engineered graphene quantum dot nanocomposite triggers α-synuclein defibrillation: Therapeutics against Parkinson’s disease. Nanomedicine 2023; 47: 102608.
12. Wu T, He K, Ang S, Ying J, Zhang S, Zhang T, et al. Impairments of spatial learning and memory following intrahippocampal injection in rats of 3-mercaptopropionic acid-modified CdTe quantum dots and molecular mechanisms. Int J Nanomedicine 2016; 11: 2737-2755.
13. Li S, Liu Z, Ji F, Xiao Z, Wang M, Peng Y, et al. Delivery of quantum dot-siRNA nanoplexes in SK-N-SH cells for BACE1 gene silencing and intracellular imaging. Mol Ther Nucleic Acids 2012; 1: e20.
14. Abdellatif AAH, Younis MA, Alsharidah M, Al Rugaie O, Tawfeek HM. Biomedical applications of quantum dots: Overview, challenges, and clinical potential. Int J Nanomedicine 2022; 17: 1951-1970.
15. Gupta R, Das S, Sinha TP, Bamzai KK. Effect of cadmium doping on electrical properties of lead nickel niobate–lead zirconate titanate [Pb1.0(Ni0.167Nb0.333Zr0.155Ti0.345)O3] ceramics. Ceramics Int 2015; 41: 13241-13249.
16. Barroso MM. Quantum dots in cell biology. J Histochem Cytochem 2011; 59: 237-251.
17. Chung S, Revia RA, Zhang M. Graphene Quantum Dots and Their Applications in Bioimaging, Biosensing, and Therapy. Adv Mater 2021; 33: e1904362.
18. Rezaei S, Meftah H-S, Ebtehajpour Y, Rahimi HR, Chamani J. Investigation on the effect of fluorescence quenching of calf thymus DNA by piperine: caspase activation in the human breast cancer cell line studies. DNA Cell Biol 2024; 43: 26-38.
19. Rezaei M, Marouzi S, Sadri K, Sammak S, Darroudi M. Biodistribution of carbon quantum dots derived from Caccinia macranthera extract via 99mTechnetium radiolabelling in rats. Inorganic Chem Commun 2025; 175: 114165.
20. Marouzi S, Sammak S, Sadri K, Darroudi M. Bioimaging comparison between synthesized carbon quantum dots and nanodiamonds. Nanomed J 2025; 12: 529-545.
21. Han L, Guo Y, Zhang H, Wang Z, Zhang F, Wang Y, et al. Preparation of carbon quantum dot fluorescent probe from waste fruit peel and its use for the detection of dopamine. RSC Adv 2024; 14: 1813-1821.
22. Kaliyaperumal P, Renganathan S, Arumugam K, Aremu BR. Engineered graphene quantum dot nanocomposite triggers α-synuclein defibrillation: Therapeutics against Parkinson’s disease. Nanomedicine 2023; 47: 102608.
23. Singh P, Singh RK, Kumar R. Journey of ZnO quantum dots from undoped to rare-earth and transition metal-doped and their applications. RSC Adv 2021; 11: 2512-2545.
24. Han M, Yi B, Song R, Wang D, Huang N, Ma Y, et al. Fucoidan-derived carbon dots as nanopenetrants of blood-brain barrier for Parkinson’s disease treatment. J Colloid Interface Sci 2025; 680: 516-527.
25. Huang C-Y, Li H, Wu Y, Lin C-H, Guan X, Hu L, et al. Inorganic halide perovskite quantum dots: a versatile nanomaterial platform for electronic applications. Nanomicro Lett 2023; 15: 16.
26. Kabel J, Sharma S, Acharya A, Zhang D, Yap YK. Molybdenum disulfide quantum dots: properties, synthesis, and applications. C 2021; 7: 45.
27. Şen A, Eroğlu Güneş C, Dursun EN, Kurar E, Kutlu S. Investigation of neuroprotective and antiapoptotic effects of rosmarinic acid in an in vitro Alzheimer’s disease model.Iran. J. Basic Med. Sci. 2026:-.
28. Lin D, Li M, Gao Y, Yin L, Guan Y. Brain-targeted gene delivery of ZnO quantum dots nanoplatform for the treatment of Parkinson disease. Chem Eng J 2022; 429: 132210.
29. Han L, Guo Y, Zhang H, Wang Z, Zhang F, Wang Y, et al. Preparation of carbon quantum dot fluorescent probe from waste fruit peel and its use for the detection of dopamine. RSC Adv 2024; 14: 1813-1821.
30. Tolou-Shikhzadeh-Yazdi S, Shakibapour N, Hosseini S, Mokaberi P, Malaekeh-Nikouei B, Chamani J. High-efficient synthesis of carbon quantum dots from orange pericarp as fluorescence turn-on probes for Ca2+ and Zn2+ ion detection and their application in trypsin activity characterization. Iran J Basic Med Sci 2023; 26: 190-199.
31. Hemmati A, Emadi H, Nabavi SR. Green synthesis of sulfur-and nitrogen-doped carbon quantum dots for determination of L-DOPA using fluorescence spectroscopy and a smartphone-based fluorimeter. ACS Omega 2023; 8: 20987-20999.
32. Guerrero ED, Lopez-Velazquez AM, Ahlawat J, Narayan M. Carbon quantum dots for treatment of amyloid disorders. ACS Appl Nano Mater 2021; 4: 2423-2433.
33. Zhou X, Hu S, Wang S, Pang Y, Lin Y, Li M. Large amino acid mimicking selenium-doped carbon quantum dots for multi-target therapy of Alzheimer’s disease. Front Pharmacol 2021; 12: 778613.
34. Mosalam EM, Elberri AI, Abdallah MS, Abdel-Bar HM, Zidan A-AA, Batakoushy HA, et al. Mechanistic insights of neuroprotective efficacy of verapamil-loaded carbon quantum dots against LPS-induced neurotoxicity in rats. Int J Mol Sci 2024; 25: 7790.
35. Liu H, Guo H, Fang Y, Wang L, Li P. Rational design of nitrogen-doped carbon dots for inhibiting β-amyloid aggregation. Molecules 2023; 28: 1451.
36. Chung YJ, Lee CH, Lim J, Jang J, Kang H, Park CB. Photomodulating carbon dots for spatiotemporal suppression of Alzheimer’s β-amyloid aggregation. ACS Nano 2020; 14: 16973-16983.
37. Dager A, Baliyan A, Kurosu S, Maekawa T, Tachibana M. Ultrafast synthesis of carbon quantum dots from fenugreek seeds using microwave plasma enhanced decomposition: Application of C-QDs to grow fluorescent protein crystals. Sci Rep 2020; 10: 12333.
38. Zhu R, Makwana KM, Zhang Y, Rajewski BH, Del Valle JR, Wang Y. Blocking tau transmission by biomimetic graphene nanoparticles. J Mater Chem B 2023; 11: 7378-7388.
39. Ysselstein D, Krainc D. Untangling alpha synuclein fibrils by graphene quantum dots. Move Disord 2018; 33: 1673.
40. Sharma S, Singh N, Nepovimova E, Korabecny J, Kuca K, Satnami ML, et al. Interaction of synthesized nitrogen enriched graphene quantum dots with novel anti-Alzheimer’s drugs: Spectroscopic insights. J Biomol Struct  Dyn 2020; 38: 1822-1837.
41. Ren C, Hu X, Zhou Q. Graphene oxide quantum dots reduce oxidative stress and inhibit neurotoxicity in vitro and in vivo through catalase‐like activity and metabolic regulation. Adv Sci 2018; 5: 1700595.
42. Walton-Raaby M, Woods R, Kalyaanamoorthy S. Investigating the theranostic potential of graphene quantum dots in Alzheimer’s disease. Int J Mol Sci 2023; 24: 9476.
43. Gómez IJ, Křížková P, Dolečková A, Cardo L, Wetzl C, Pizúrová N, et al. Multifunctional graphene quantum dots: A therapeutic strategy for neurodegenerative diseases by regulating calcium influx, crossing the blood-brain barrier and inhibiting Aβ-protein aggregation. Appl Mater Today 2024; 36: 102072.
44. Kim D, Yoo JM, Hwang H, Lee J, Lee SH, Yun SP, et al. Graphene quantum dots prevent α-synucleinopathy in Parkinson’s disease. Nat Nanotechnol 2018; 13: 812-818.
45. Zhao D, Song H, Hao L, Liu X, Zhang L, Lv Y. Luminescent ZnO quantum dots for sensitive and selective detection of dopamine. Talanta 2013; 107: 133-139.
46. Abd Elmonem HA, Morsi RM, Mansour DS, El-Sayed E-SR. Myco-fabricated ZnO nanoparticles ameliorate neurotoxicity in mice model of Alzheimer’s disease via acetylcholinesterase inhibition and oxidative stress reduction. Biometals 2023; 36: 1391-1404.
47. Sobhani Z, Khalifeh R, Banizamani M, Rajabzadeh M. Water-soluble ZnO quantum dots modified by polyglycerol: The pH-sensitive and targeted fluorescent probe for delivery of an anticancer drug. J Drug Deliv Sci Technol 2022; 76: 103452.
48. Yang Z, Dong Y, Zong S, Li L, Yang K, Wang Z, et al. Water-dispersed CsPbBr 3 nanocrystals for single molecule localization microscopy with high location accuracy for targeted bioimaging. Nanoscale 2022; 14: 6392-6401.
49. He M, Zhang X, Ran X, Zhang Y, Nie X, Xiao B, et al. Black phosphorus nanosheets protect neurons by degrading aggregative α‐syn and clearing ROS in parkinson’s disease. Adv Mater 2024; 36: 2404576.
50. Bu Y, Zhang M, Fu J, Yang X, Liu S. Black phosphorous quantum dots for signal-on cathodic photoelectrochemical aptasensor monoitoring amyloid β peptide. Anal Chim Acta 2022; 1189: 339200.
51. Xiong S, Li Z, Liu Y, Wang Q, Luo J, Chen X, et al. Brain-targeted delivery shuttled by black phosphorus nanostructure to treat Parkinson’s disease. Biomaterials 2020; 260: 120339.
52. Guo S, Zhang Z, Xu B, Wang M, Fan T, Zhong X, et al. Black phosphorus microbubbles combined with ultrasound for treating Parkinson’s disease. Adv Ther 2024; 7: 2300254.
53. Chi J, Xue Y, Zhou Y, Han T, Ning B, Cheng L, et al. Perovskite probe-based machine learning imaging model for rapid pathologic diagnosis of cancers. ACS Nano 2024; 18: 24295-24305.
54. Tosat-Bitrián C, Avis-Bodas A, Porras G, Borrego-Hernández D, García-Redondo A, Martín-Requero A, et al. Cdse quantum dots in human models derived from als patients: Characterization, nuclear penetration studies and multiplexing. Nanomaterials 2021; 11: 671.
55. Luo F, Li S, Cui L, Zu Y, Chen Y, Huang D, et al. Biocompatible perovskite quantum dots with superior water resistance enable long-term monitoring of the H2S level in vivo. Nanoscale 2021; 13: 14297-14303.
56. Lu X, Hou X, Tang H, Yi X, Wang J. A high-quality CdSe/CdS/ZnS quantum-dot-based FRET aptasensor for the simultaneous detection of two different Alzheimer’s disease core biomarkers. Nanomaterials 2022; 12: 4031.
57. Huang N, Cheng S, Zhang X, Tian Q, Pi J, Tang J, et al. Efficacy of NGR peptide-modified PEGylated quantum dots for crossing the blood–brain barrier and targeted fluorescence imaging of glioma and tumor vasculature. Nanomedicine 2017; 13: 83-93.
58. Yeo H-G, Won J, Gwon LW, Roh S, Lee W-J, Lim KS, et al. CdSe quantum dot-based delivery system for CRISPR-Cas9 mediated microglial gene modulation. ACS Appl Nano Mater 2024; 7: 24013-24027.
59. Hess KL, Oh E, Tostanoski LH, Andorko JI, Susumu K, Deschamps JR, et al. Engineering immunological tolerance using quantum dots to tune the density of self‐antigen display. Adv Funct Mater 2017; 27: 1700290.
60. Li Y, Tang H, Zhu H, Kakinen A, Wang D, Andrikopoulos N, et al. Ultrasmall molybdenum disulfide quantum dots cage Alzheimer’s amyloid beta to restore membrane fluidity. ACS Appl Mater Interfaces 2021; 13: 29936-29948.
61. Gao W, Wang W, Dong X, Sun Y. Nitrogen‐doped carbonized polymer dots: A potent scavenger and detector targeting Alzheimer’s β‐amyloid plaques. Small 2020; 16: 2002804.
62. Yu S, Choi J, Ahn Y-R, Kim M, Kim N, Lee H, et al. Ultra-sensitive nanoplatform for detection of brain-derived neurotrophic factor using silica-coated gold nanoparticles with enzyme-formed quantum dots. Molecules 2025; 30: 699.
63. Shi L, Huanood G, Miura S, Kuragano M, Tokuraku K. Real-time 3D imaging and inhibition analysis of human serum amyloid A aggregations using quantum dots. Int J Mol Sci 2024; 25: 11128.
64. Agarwal R, Domowicz MS, Schwartz NB, Henry J, Medintz I, Delehanty JB, et al. Delivery and tracking of quantum dot peptide bioconjugates in an intact developing avian brain. ACS Chem Neurosci 2015; 6: 494-504.
65. Jackson H, Muhammad O, Daneshvar H, Nelms J, Popescu A, Vogelbaum MA, et al. Quantum dots are phagocytized by macrophages and colocalize with experimental gliomas. Neurosurgery 2007; 60: 524-530.
66. Wen C-J, Zhang L-W, Al-Suwayeh SA, Yen T-C, Fang J-Y. Theranostic liposomes loaded with quantum dots and apomorphine for brain targeting and bioimaging. Int J Nanomedicine 2012; 7: 1599-1611.
67. Wang F, He M, Huang B, Tang T, Liu F, Cui R, et al. Band gap engineering improves three-photon luminescence of quantum dots for deep brain imaging. Anal Chem 2023; 95: 10947-10956.
68. Connor T, Weerasinghe H, Lathia J, Burda C, Yildirim M, editors. Advances in deep brain imaging with quantum dots: Structural, functional, and disease-specific roles. Photonics 2025; 12: 3.
69. Tong S, Zhong J, Chen X, Deng X, Huang J, Zhang Y, et al. In vivo deep-brain 3-and 4-photon fluorescence imaging of subcortical structures labeled by quantum dots excited at the 2200 nm window. ACS Nano 2023; 17: 3686-3695.
70. Ricard C, Lamasse L, Jaouen A, Rougon G, Debarbieux F. Combination of an optical parametric oscillator and quantum-dots 655 to improve imaging depth of vasculature by intravital multicolor two-photon microscopy. Biomed Opt Express 2016; 7: 2362-2372.
71. Jiao M, Li X, Liu H, Cai P, Yang X, McHugh KJ, et al. Aqueous grown quantum dots with robust near-infrared fluorescence for integrated traumatic brain injury diagnosis and surgical monitoring. ACS Nano 2024; 18: 19038-19053.
72. Huang B, Tang T, Chen S-H, Li H, Sun Z-J, Zhang Z-L, et al. Near-infrared-IIb emitting single-atom catalyst for imaging-guided therapy of blood-brain barrier breakdown after traumatic brain injury. Nat Commun 2023; 14: 197.
73. Longhurst JK, Rider JV, Cummings JL, John SE, Poston B, Held Bradford EC, et al. A novel way of measuring dual-task interference: The reliability and construct validity of the dual-task effect battery in neurodegenerative disease. Neurorehabil Neural Repair 2022; 36: 346-359.
74. Alizadeh Nobari S, Doustvandi MA, Yaghoubi SM, Shahriar Oskouei SS, Alizadeh E, Afrashteh Nour M, et al. Emerging trends in quantum dot-based photosensitizers for enhanced photodynamic therapy in cancer treatment. J Pharm Investig 2025; 55: 55-90.
75. Doustvandi MA, Mohammadnejad F, Mansoori B, Tajalli H, Mohammadi A, Mokhtarzadeh A, et al. Photodynamic therapy using zinc phthalocyanine with low dose of diode laser combined with doxorubicin is a synergistic combination therapy for human SK-MEL-3 melanoma cells. Photodiagnosis Photodyn Ther 2019; 28: 88-97.
76. Vellekoop IM, Mosk AP. Focusing coherent light through opaque strongly scattering media. Opt Lett 2007; 32: 2309-2311.
77. Beer. Bestimmung der Absorption des rothen Lichts in farbigen Flüssigkeiten. Annalen der Physik 1852; 162: 78-88.
78. Hee MR, Izatt JA, Swanson EA, Huang D, Schuman JS, Lin CP, et al. Optical coherence tomography of the human retina. Arch Ophthalmol 1995; 113: 325-332.
79. Drobizhev M, Tillo S, Makarov N, Hughes T, Rebane A. Absolute two-photon absorption spectra and two-photon brightness of orange and red fluorescent proteins. J Phys Chem B 2009; 113: 855-859.
80. Karatum O, Kaleli HN, Eren GO, Sahin A, Nizamoglu S. Electrical stimulation of neurons with quantum dots via near-infrared light. ACS Nano 2022; 16: 8233-8243.
81. Sakmann B, Edwards F, Konnerth A, Takahashi T. Patch clamp techniques used for studying synaptic transmission in slices of mammalian brain. Q J Exp Physiol 1989; 74: 1107-1118.
82. Tsytsarev V, Liao L-D, Kong KV, Liu Y-H, Erzurumlu RS, Olivo M, et al. Recent progress in voltage-sensitive dye imaging for neuroscience. J Nanosci Nanotechnol 2014; 14: 4733-4744.
83. Theer P, Denk W. On the fundamental imaging-depth limit in two-photon microscopy. J Opt Soc Am A 2006; 23: 3139-3149.
84. Streich L, Boffi JC, Wang L, Alhalaseh K, Barbieri M, Rehm R, et al. High-resolution structural and functional deep brain imaging using adaptive optics three-photon microscopy. Nat Methods 2021; 18: 1253-1258.
85. Chakraborty P, Das SS, Dey A, Chakraborty A, Bhattacharyya C, Kandimalla R, et al. Quantum dots: The cutting-edge nanotheranostics in brain cancer management. J Control Release 2022; 350: 698-715.
86. Smith AM, Duan H, Mohs AM, Nie S. Bioconjugated quantum dots for in vivo molecular and cellular imaging. Adv Drug Deliv Rev 2008; 60: 1226-1240.
87. Medintz IL, Uyeda HT, Goldman ER, Mattoussi H. Quantum dot bioconjugates for imaging, labelling and sensing. Nat Mate 2005; 4: 435-446.
88. Michalet X, Pinaud FF, Bentolila LA, Tsay JM, Doose S, Li JJ, et al. Quantum dots for live cells, in vivo imaging, and diagnostics. Science 2005; 307: 538-544.
89. Paris-Robidas S, Brouard D, Emond V, Parent M, Calon F. Internalization of targeted quantum dots by brain capillary endothelial cells in vivo. J Cereb Blood Flow Metab 2016; 36: 731-742.
90. Zarei A, Rezaei A, Shahlaei M, Asani Z, Ramazani A, Wang C. Selective and sensitive CQD-based sensing platform for Cu2+ detection in Wilson’s disease. Sci Rep 2024; 14: 13183.
91. Ma X, Hu Q, Yuan J, Feng Y, Cheng Z. Glutathione modified silicon-doped carbon quantum dots as a sensitive fluorescent probe for ClO− detection. J Fluoresc 2025; 35: 3529-3538.
Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 05 August 2026