REFERENCES
1. Peller, J. R.; Mezyk, S. P.; Shidler, S.; et al. Facile nanoplastics formation from macro and microplastics in aqueous media. Environ. Pollut. 2022, 313, 120171.
2. Ma, Y. B.; Xie, Z. Y.; Hamid, N.; et al. Recent advances in micro (nano) plastics in the environment: distribution, health risks, challenges and future prospects. Aquat. Toxicol. 2023, 261, 106597.
3. Nie, X.; Xing, X.; Xie, R.; et al. Impact of iron/aluminum (hydr)oxide and clay minerals on heteroaggregation and transport of nanoplastics in aquatic environment. J. Hazard. Mater. 2023, 446, 130649.
4. Enfrin, M.; Hachemi, C.; Hodgson, P. D.; et al. Nano/micro plastics - Challenges on quantification and remediation: a review. J. Water. Process. Eng. 2021, 42, 102128.
5. Sun, A.; Wang, W. X. Human exposure to microplastics and its associated health risks. Environ. Health. 2023, 1, 139-49.
6. Cheng, H.; Duan, Z.; Wu, Y.; et al. Immunotoxicity responses to polystyrene nanoplastics and their related mechanisms in the liver of zebrafish (Danio rerio) larvae. Environ. Int. 2022, 161, 107128.
7. Nihart, A. J.; Garcia, M. A.; El Hayek, E.; et al. Bioaccumulation of microplastics in decedent human brains. Nat. Med. 2025, 31, 1114-9.
8. Junaid, M.; Abbas, Z.; Siddiqui, J. A.; et al. Ecotoxicological impacts associated with the interplay between micro(nano)plastics and pesticides in aquatic and terrestrial environments. TrAC. Trends. Anal. Chem. 2023, 165, 117133.
9. Qiu, X.; Li, L.; Qiu, Q.; et al. Medical exposure to micro(nano)plastics: an exposure pathway with potentially significant harm to human health that should not be overlooked. Sci. Total. Environ. 2024, 957, 177743.
10. Nazeer, N.; Bhargava, A.; Soni, N.; Tiwari, R.; Ratre, P.; Mishra, P. K. Unravelling the molecular dimensions of atmospheric micro(nano)plastics: exploring potential impacts on human health and strategies for detection. Phys. Chem. Earth. 2024, 135, 103604.
11. Xie, J.; Ji, J.; Sun, Y.; Ma, Y.; Wu, D.; Zhang, Z. Blood-brain barrier damage accelerates the accumulation of micro- and nanoplastics in the human central nervous system. J. Hazard. Mater. 2024, 480, 136028.
12. Paing, Y. M. M.; Eom, Y.; Song, G. B.; et al. Neurotoxic effects of polystyrene nanoplastics on memory and microglial activation: insights from in vivo and in vitro studies. Sci. Total. Environ. 2024, 924, 171681.
13. Jeong, A.; Park, S. J.; Lee, E. J.; Kim, K. W. Nanoplastics exacerbate Parkinson’s disease symptoms in C. elegans and human cells. J. Hazard. Mater. 2024, 465, 133289.
14. Wang, Y.; Wang, J.; Cong, J.; et al. Nanoplastics induce neuroexcitatory symptoms in zebrafish (Danio rerio) larvae through a manner contrary to Parkinsonian’s way in proteomics. Sci. Total. Environ. 2023, 905, 166898.
15. Rudroff, T. Artificial intelligence as a replacement for animal experiments in neurology: potential, progress, and challenges. Neurol. Int. 2024, 16, 805-20.
16. Vorhees, C. V.; Williams, M. T.; Hawkey, A. B.; Levin, E. D. Translating neurobehavioral toxicity across species from zebrafish to rats to humans: implications for risk assessment. Front. Toxicol. 2021, 3, 629229.
17. Mazarati, A. Can we and should we use animal models to study neurobehavioral comorbidities of epilepsy? Epilepsy. Behav. 2019, 101, 106566.
18. Majumder, J.; Murphy, W. L. Neural organoids as advanced tools for neurotoxicity modeling. Curr. Res. Toxicol. 2025, 9, 100249.
19. Li, T.; Qin, X.; Ao, Q. Research progress on neural cell culture systems. Curr. Neuropharmacol. 2025, 23, 1518-32.
20. Kaawa-Mafigiri, D.; Ekusai Sebatta, D.; Munabi, I.; Mwaka, E. S. Genetic and genomic researchers’ perspectives on biological sample sharing in collaborative research in Uganda: a qualitative study. J. Empir. Res. Hum. Res. Ethics. 2023, 18, 134-46.
21. Sakaguchi, H. Self-organization and applications of neural organoids. Eur. J. Cell. Biol. 2025, 104, 151496.
22. Zhao, Y.; Wang, T.; Liu, J.; Wang, Z.; Lu, Y. Emerging brain organoids: 3D models to decipher, identify and revolutionize brain. Bioact. Mater. 2025, 47, 378-402.
23. Qian, X.; Song, H.; Ming, G. L. Brain organoids: advances, applications and challenges. Development 2019, 146, dev166074.
24. Di Stefano, J.; Di Marco, F.; Cicalini, I.; et al. Generation, interrogation, and future applications of microglia-containing brain organoids. Neural. Regen. Res. 2025, 20, 3448-60.
25. Nguyen, X. H.; Yoo, J. Current status and future prospects of toxicity assessment using organoids. Toxicol. Res. 2025, 41, 325-33.
26. Kwak, T.; Park, S. H.; Lee, S.; et al. Guidelines for manufacturing and application of organoids: brain. Int. J. Stem. Cells. 2024, 17, 158-81.
27. Vaez Ghaemi, R.; Co, I. L.; McFee, M. C.; Yadav, V. G. Brain organoids: a new, transformative investigational tool for neuroscience research. Adv. Biosyst. 2019, 3, e1800174.
28. Hongen, T.; Sakai, K.; Ito, T.; Qin, X. Y.; Sone, H. Human-induced pluripotent stem cell-derived neural organoids as a novel in vitro platform for developmental neurotoxicity assessment. Int. J. Mol. Sci. 2024, 25, 12523.
29. Cao, Y. The uses of 3D human brain organoids for neurotoxicity evaluations: a review. Neurotoxicology 2022, 91, 84-93.
30. Sun, N.; Meng, X.; Liu, Y.; Song, D.; Jiang, C.; Cai, J. Applications of brain organoids in neurodevelopment and neurological diseases. J. Biomed. Sci. 2021, 28, 30.
31. Zhang, Z.; O’Laughlin, R.; Song, H.; Ming, G. L. Patterning of brain organoids derived from human pluripotent stem cells. Curr. Opin. Neurobiol. 2022, 74, 102536.
32. Wang, M.; Gage, F. H.; Schafer, S. T. Transplantation strategies to enhance maturity and cellular complexity in brain organoids. Biol. Psychiatry. 2023, 93, 616-21.
33. Ji, X. S.; Ji, X. L.; Xiong, M.; Zhou, W. H. Modeling congenital brain malformations with brain organoids: a narrative review. Transl. Pediatr. 2023, 12, 68-78.
34. Kim, S. J.; Jung, W. H.; Choe, M. S.; Jeon, Y. S.; Lee, M. Y. Modeling synucleinopathy using hESC-derived cerebral organoids. Cells 2025, 14, 1436.
35. Wang, Y.; Wang, L.; Guo, Y.; Zhu, Y.; Qin, J. Engineering stem cell-derived 3D brain organoids in a perfusable organ-on-a-chip system. RSC. Adv. 2018, 8, 1677-85.
36. Xu, J.; Wen, Z. Brain organoids: studying human brain development and diseases in a dish. Stem. Cells. Int. 2021, 2021, 5902824.
37. Ao, Z.; Cai, H.; Wu, Z.; et al. Tubular human brain organoids to model microglia-mediated neuroinflammation. Lab. Chip. 2021, 21, 2751-62.
38. Tian, C.; Cai, H.; Ao, Z.; et al. Engineering human midbrain organoid microphysiological systems to model prenatal PFOS exposure. Sci. Total. Environ. 2024, 947, 174478.
39. Babu, H. W. S.; Kumar, S. M.; Kaur, H.; Iyer, M.; Vellingiri, B. Midbrain organoids for Parkinson’s disease (PD) - a powerful tool to understand the disease pathogenesis. Life. Sci. 2024, 345, 122610.
40. Monzel, A. S.; Hemmer, K.; Kaoma, T.; et al. Machine learning-assisted neurotoxicity prediction in human midbrain organoids. Parkinsonism. Relat. Disord. 2020, 75, 105-9.
41. Smits, L. M.; Schwamborn, J. C. Midbrain organoids: a new tool to investigate Parkinson’s disease. Front. Cell. Dev. Biol. 2020, 8, 359.
42. Han, Y.; Yu, Z.; Chen, Y.; et al. PM2.5 induces developmental neurotoxicity in cortical organoids. Environ. Pollut. 2024, 361, 124913.
43. Kim, Y.; Kim, H.; Cho, B.; et al. Modeling APOE ε4 familial Alzheimer’s disease in directly converted 3D brain organoids. Front. Aging. Neurosci. 2024, 16, 1435445.
44. Choe, M. S.; Yeo, H. C.; Kim, J. S.; et al. Simple modeling of familial Alzheimer’s disease using human pluripotent stem cell-derived cerebral organoid technology. Stem. Cell. Res. Ther. 2024, 15, 118.
45. Lu, S.; Zhu, X.; Zeng, P.; et al. Exposure to PFOA, PFOS, and PFHxS induces Alzheimer’s disease-like neuropathology in cerebral organoids. Environ. Pollut. 2024, 363, 125098.
46. Latoszek, E.; Czeredys, M. Molecular components of store-operated calcium channels in the regulation of neural stem cell physiology, neurogenesis, and the pathology of Huntington’s disease. Front. Cell. Dev. Biol. 2021, 9, 657337.
47. Smirnova, L.; Hartung, T. The promise and potential of brain organoids. Adv. Healthc. Mater. 2024, 13, e2302745.
48. Hong, Y. J.; Lee, S. B.; Choi, J.; Yoon, S. H.; Do, J. T. A simple method for generating cerebral organoids from human pluripotent stem cells. Int. J. Stem. Cells. 2022, 15, 95-103.
49. de Jong, J. O.; Llapashtica, C.; Genestine, M.; et al. Cortical overgrowth in a preclinical forebrain organoid model of CNTNAP2-associated autism spectrum disorder. Nat. Commun. 2021, 12, 4087.
50. Bilinovich, S. M.; Uhl, K. L.; Lewis, K.; et al. Integrated RNA sequencing reveals epigenetic impacts of diesel particulate matter exposure in human cerebral organoids. Dev. Neurosci. 2020, 42, 195-207.
51. Chang, X.; Li, J.; Niu, S.; Xue, Y.; Tang, M. Neurotoxicity of metal-containing nanoparticles and implications in glial cells. J. Appl. Toxicol. 2021, 41, 65-81.
52. Adamiak, K.; Sidoryk-Węgrzynowicz, M.; Dąbrowska-Bouta, B.; Sulkowski, G.; Strużyńska, L. Primary astrocytes as a cellular depot of polystyrene nanoparticles. Sci. Rep. 2025, 15, 6502.
53. Gong, J. Y.; Holt, M. G.; Hoet, P. H. M.; Ghosh, M. Neurotoxicity of four frequently used nanoparticles: a systematic review to reveal the missing data. Arch. Toxicol. 2022, 96, 1141-212.
54. Wang, Y.; Cong, J.; Kong, X.; et al. Positively charged nanoplastics destruct the structure of the PCK1 enzyme, promote the aerobic gycolysis pathway, and induce hepatic tumor risks. Environ. Sci. Technol. 2025, 59, 3013-23.
55. Shan, S.; Zhang, Y.; Zhao, H.; Zeng, T.; Zhao, X. Polystyrene nanoplastics penetrate across the blood-brain barrier and induce activation of microglia in the brain of mice. Chemosphere 2022, 298, 134261.
56. Urani, C.; Barbieri, R.; Alloisio, S.; Tesauro, M. From the environment to molecular interactions of nanoplastics: unraveling the neurotoxic impacts and the implications in neurodegenerative processes. Appl. Sci. 2024, 14, 7280.
57. Tan, C.; Kang, C.; Liu, P.; Sun, Y.; Jin, H. Polystyrene nanoplastics exposure trigger cognitive impairment mitigated by luteolin modulated glucose-6-phosphate dehydrogenase/glutathione-dependent pathway. J. Hazard. Mater. 2025, 493, 138404.
58. Bai, H.; Wu, Y.; Li, H.; et al. Cerebral neurotoxicity of amino-modified polystyrene nanoplastics in mice and the protective effects of functional food Camellia pollen. Sci. Total. Environ. 2024, 912, 169511.
59. Jeong, H.; Shanmugiah, J.; Jang, J.; Lee, D. H.; Choi, J.; Kim, J. S. Nanoplastics cause an increased risk of Parkinson’s disease compared to microplastics at environmental exposure levels. J. Hazard. Mater. Adv. 2025, 20, 100941.
60. Cong, J.; Wu, J.; Fang, Y.; et al. Application of organoid technology in the human health risk assessment of microplastics: a review of progresses and challenges. Environ. Int. 2024, 188, 108744.
61. Abdulla, A.; Yan, H.; Chen, S.; et al. A multichannel microfluidic device for revealing the neurotoxic effects of Bisphenol S on cerebral organoids under low-dose constant exposure. Biosens. Bioelectron. 2025, 267, 116754.
62. Tao, M.; Wang, C.; Zheng, Z.; et al. Nanoplastics exposure-induced mitochondrial dysfunction contributes to disrupted stem cell differentiation in human cerebral organoids. Ecotoxicol. Environ. Saf. 2024, 285, 117063.
63. Park, S. B.; Jo, J. H.; Kim, S. S.; et al. Microplastics accumulation induces kynurenine-derived neurotoxicity in cerebral organoids and mouse brain. Biomol. Ther. 2025, 33, 447-57.
64. Huang, F.; You, H.; Tang, X.; et al. Early-life exposure to polypropylene nanoplastics induces neurodevelopmental toxicity in mice and human iPSC-derived cerebral organoids. J. Nanobiotechnology. 2025, 23, 474.
65. Hua, T.; Kiran, S.; Li, Y.; Sang, Q. A. Microplastics exposure affects neural development of human pluripotent stem cell-derived cortical spheroids. J. Hazard. Mater. 2022, 435, 128884.
66. Chen, S.; Chen, Y.; Gao, Y.; et al. Toxic effects and mechanisms of nanoplastics on embryonic brain development using brain organoids model. Sci. Total. Environ. 2023, 904, 166913.
67. Kim, S.; Lee, Y.; Lee, H. A.; Lee, M. O. SiO2 nanoparticles disrupt neurodevelopmental processes in human midbrain organoids in a redox-suppressed, non-cytotoxic manner. J. Hazard. Mater. 2026, 501, 140670.
68. Wu, X.; Kreutz, A.; Dixon, D.; Tokar, E. J. Engineering human cerebral organoids to explore mechanisms of arsenic-induced developmental neurotoxicity. Toxicol. Appl. Pharmacol. 2025, 496, 117230.
69. Bu, Q.; Huang, Y.; Li, M.; et al. Acrylamide exposure represses neuronal differentiation, induces cell apoptosis and promotes tau hyperphosphorylation in hESC-derived 3D cerebral organoids. Food. Chem. Toxicol. 2020, 144, 111643.
70. Li, J.; Weng, H.; Liu, S.; et al. Embryonic exposure of polystyrene nanoplastics affects cardiac development. Sci. Total. Environ. 2024, 906, 167406.
71. Li, M.; Gao, X.; Lan, Y.; et al. Revealing the neurodevelopmental toxicity of face mask-derived microplastics to humans based on neural organoids. J. Hazard. Mater. 2025, 492, 138084.
72. Bhattacharyya, S.; Greer, M. L.; Salehi, M. Impact of micro- and nanoplastics exposure on human health: focus on neurological effects from ingestion. Front. Public. Health. 2025, 13, 1681776.
73. Lin, Z.; Wang, W.; Liu, R.; et al. Cyborg organoids integrated with stretchable nanoelectronics can be functionally mapped during development. Nat. Protoc. 2025, 20, 2528-59.
74. Huang, H.; Hou, J.; Xi, B. The need to implement innovative technologies to advance research on the biotoxicity of micro- and nanoplastics. Environ. Health. 2025, 3, 1429-37.
75. Kistemaker, L.; van Bodegraven, E. J.; de Vries, H. E.; Hol, E. M. Vascularized human brain organoids: current possibilities and prospects. Trends. Biotechnol. 2025, 43, 1275-85.
76. Depla, J. A.; Mulder, L. A.; de Sá, R. V.; et al. Human brain organoids as models for central nervous system viral infection. Viruses 2022, 14, 634.
77. Jeong, E.; Choi, S.; Cho, S. W. Recent advances in brain organoid technology for human brain research. ACS. Appl. Mater. Interfaces. 2023, 15, 200-19.
78. Makrygianni, E. A.; Chrousos, G. P. From brain organoids to networking assembloids: Implications for neuroendocrinology and stress medicine. Front. Physiol. 2021, 12, 621970.
79. Kim, S. H.; Chang, M. Y. Application of human brain organoids-opportunities and challenges in modeling human brain development and neurodevelopmental diseases. Int. J. Mol. Sci. 2023, 24, 12528.
