REFERENCES
2. Sun C, Sha S, Shan Y, et al. Intranasal delivery of BACE1 siRNA and berberine via engineered stem cell exosomes for the treatment of Alzheimer’s disease. Int J Nanomedicine. 2025;20:5873-91.
3. Peng L, Bestard-Lorigados I, Song W. The synapse as a treatment avenue for Alzheimer’s Disease. Mol Psychiatry. 2022;27:2940-9.
4. Reiss AB, Glass AD, Wisniewski T, et al. Alzheimer’s disease: many failed trials, so where do we go from here? J Investig Med. 2020;68:1135-40.
5. Williams JB, Cao Q, Yan Z. Transcriptomic analysis of human brains with Alzheimer’s disease reveals the altered expression of synaptic genes linked to cognitive deficits. Brain Commun. 2021;3:fcab123.
6. Zhang R, Song Y, Su X. Necroptosis and Alzheimer’s disease: pathogenic mechanisms and therapeutic opportunities. J Alzheimers Dis. 2023;94:S367-86.
7. Xie W, Guo D, Li J, et al. CEND1 deficiency induces mitochondrial dysfunction and cognitive impairment in Alzheimer’s disease. Cell Death Differ. 2022;29:2417-28.
8. Wang C, Zong S, Cui X, et al. The effects of microglia-associated neuroinflammation on Alzheimer’s disease. Front Immunol. 2023;14:1117172.
9. Morrone CD, Raghuraman R, Hussaini SA, Yu WH. Proteostasis failure exacerbates neuronal circuit dysfunction and sleep impairments in Alzheimer’s disease. Mol Neurodegener. 2023;18:27.
10. Yang P, Sun F. Aducanumab: the first targeted Alzheimer’s therapy. Drug Discov Ther. 2021;15:166-8.
11. Khan B, Iqbal MK, Khan MA, et al. Unraveling the complexity of Alzheimer’s disease: insights into etiology and advancements in treatment strategies. J Mol Neurosci. 2025;75:57.
12. Wang J, Chen D, Ho EA. Challenges in the development and establishment of exosome-based drug delivery systems. J Control Release. 2021;329:894-906.
13. Alzhrani GN, Alanazi ST, Alsharif SY, et al. Exosomes: isolation, characterization, and biomedical applications. Cell Biol Int. 2021;45:1807-31.
14. Sardar Sinha M, Ansell-Schultz A, Civitelli L, et al. Alzheimer’s disease pathology propagation by exosomes containing toxic amyloid-beta oligomers. Acta Neuropathol. 2018;136:41-56.
15. Yuyama K, Sun H, Mitsutake S, Igarashi Y. Sphingolipid-modulated exosome secretion promotes clearance of amyloid-β by microglia. J Biol Chem. 2012;287:10977-89.
16. Li D, Wang Y, Jin X, et al. NK cell-derived exosomes carry miR-207 and alleviate depression-like symptoms in mice. J Neuroinflammation. 2020;17:126.
17. Kaur S, Verma H, Dhiman M, et al. Brain exosomes: friend or foe in Alzheimer’s Disease? Mol Neurobiol. 2021;58:6610-24.
18. Chen H, Deng C, Meng Z, et al. Combined catalpol and tetramethylpyrazine promote axonal plasticity in Alzheimer’s disease by inducing astrocytes to secrete exosomes carrying CDK5 mRNA and regulating STAT3 phosphorylation. Mol Neurobiol. 2024;61:10770-91.
19. Cai H, Pang Y, Wang Q, et al. Proteomic profiling of circulating plasma exosomes reveals novel biomarkers of Alzheimer’s disease. Alzheimers Res Ther. 2022;14:181.
20. McKeever PM, Schneider R, Taghdiri F, et al. MicroRNA expression levels are altered in the cerebrospinal fluid of patients with young-onset Alzheimer’s disease. Mol Neurobiol. 2018;55:8826-41.
21. Duan L, Ouyang K, Wang J, et al. Exosomes as targeted delivery platform of CRISPR/Cas9 for therapeutic genome editing. Chembiochem. 2021;22:3360-8.
22. Iyaswamy A, Thakur A, Guan XJ, et al. Fe65-engineered neuronal exosomes encapsulating corynoxine-B ameliorate cognition and pathology of Alzheimer’s disease. Signal Transduct Target Ther. 2023;8:404.
23. Atya HB, Sharaf NM, Abdelghany RM, El-Helaly SN, Taha H. Autophagy and exosomes; inter-connected maestros in Alzheimer’s disease. Inflammopharmacology. 2024;32:2061-73.
24. Kathait P, Patel PK, Sahu AN. Harnessing exosomes and plant-derived exosomes as nanocarriers for the efficient delivery of plant bioactives. Nanomedicine (Lond). 2024;19:2679-97.
25. Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013;200:373-83.
26. Suga K, Matsui D, Watanabe N, Okamoto Y, Umakoshi H. Insight into the exosomal membrane: from viewpoints of membrane fluidity and polarity. Langmuir. 2021;37:11195-202.
27. Choi DS, Kim DK, Kim YK, Gho YS. Proteomics, transcriptomics and lipidomics of exosomes and ectosomes. Proteomics. 2013;13:1554-71.
28. Cui Z, Amevor FK, Zhao X, et al. Potential therapeutic effects of milk-derived exosomes on intestinal diseases. J Nanobiotechnol. 2023;21:496.
29. Hu Q, Su H, Li J, et al. Clinical applications of exosome membrane proteins. Precis Clin Med. 2020;3:54-66.
30. You Y, Muraoka S, Jedrychowski MP, et al. Human neural cell type-specific extracellular vesicle proteome defines disease-related molecules associated with activated astrocytes in Alzheimer’s disease brain. J Extracell Vesicles. 2022;11:e12183.
31. Li Y, Hu C, Zhai P, et al. Fibroblastic reticular cell-derived exosomes are a promising therapeutic approach for septic acute kidney injury. Kidney Int. 2024;105:508-23.
32. Liang Y, Duan L, Lu J, Xia J. Engineering exosomes for targeted drug delivery. Theranostics. 2021;11:3183-95.
33. Verma H, Kaur S, Jeeth P, et al. Understanding Aβ(25-35) peptide altered exosomal proteome and associated pathways linked with the Alzheimer’s disease pathogenesis using human neuroblastoma SH-SY5Y cells. Metab Brain Dis. 2024;40:25.
34. Song Z, Xu Y, Deng W, et al. Brain derived exosomes are a double-edged sword in Alzheimer’s disease. Front Mol Neurosci. 2020;13:79.
35. Mehrabadi S. Extracellular vesicles: a promising therapeutic approach to Alzheimer’s disease. Curr Alzheimer Res. 2024;21:615-24.
37. Zhao M, Li Q, Chai Y, et al. An anti-CD19-exosome delivery system navigates the blood-brain barrier for targeting of central nervous system lymphoma. J Nanobiotechnol. 2025;23:173.
38. Kapogiannis D. Exosome biomarkers revolutionize preclinical diagnosis of neurodegenerative diseases and assessment of treatment responses in clinical trials. Adv Exp Med Biol. 2020;1195:149.
39. Kuroda H, Tachikawa M, Yagi Y, et al. Cluster of differentiation 46 is the major receptor in human blood-brain barrier endothelial cells for uptake of exosomes derived from brain-metastatic melanoma cells (SK-Mel-28). Mol Pharm. 2019;16:292-304.
40. Matsumoto J, Stewart T, Sheng L, et al. Transmission of α-synuclein-containing erythrocyte-derived extracellular vesicles across the blood-brain barrier via adsorptive mediated transcytosis: another mechanism for initiation and progression of Parkinson's disease? Acta Neuropathol Commun. 2017;5:71.
41. Liu B, Su Y, Sun H, et al. Vamp3/syntaxin 4 mediates the basolateral membrane fusion of TfR transcytosis across the BBB and is exploited by pathogenic E. coli. Proc Natl Acad Sci U S A. 2025;122:e2500285122.
42. Yang T, Martin P, Fogarty B, et al. Exosome delivered anticancer drugs across the blood-brain barrier for brain cancer therapy in Danio rerio. Pharm Res. 2015;32:2003-14.
43. Banks WA, Sharma P, Bullock KM, Hansen KM, Ludwig N, Whiteside TL. Transport of extracellular vesicles across the blood-brain barrier: brain pharmacokinetics and effects of inflammation. Int J Mol Sci. 2020;21:4407.
44. Liang X, Fa W, Wang N, et al. Exosomal miR-532-5p induced by long-term exercise rescues blood-brain barrier function in 5XFAD mice via downregulation of EPHA4. Aging Cell. 2023;22:e13748.
45. Kim Y, Lee S, Zhang H, et al. CLEC14A deficiency exacerbates neuronal loss by increasing blood-brain barrier permeability and inflammation. J Neuroinflammation. 2020;17:48.
46. Beltran-Velasco AI, Clemente-Suárez VJ. Impact of peripheral inflammation on blood-brain barrier dysfunction and its role in neurodegenerative diseases. Int J Mol Sci. 2025;26:2440.
47. Elashiry M, Carroll A, Yuan J, et al. Oral microbially-induced small extracellular vesicles cross the blood-brain barrier. Int J Mol Sci. 2024;25:4509.
48. Sandoval H, Ibáñez B, Contreras M, et al. Extracellular vesicles from preeclampsia disrupt the blood-brain barrier by reducing CLDN5. Arterioscler, Thromb, Vasc Biol. 2025;45:298-311.
49. Zhdanova DY, Poltavtseva RA, Svirshchevskaya EV, Bobkova NV. Effect of intranasal administration of multipotent mesenchymal stromal cell exosomes on memory of mice in Alzheimer’s disease model. Bull Exp Biol Med. 2021;170:575-82.
50. Guo M, Yin Z, Chen F, Lei P. Mesenchymal stem cell-derived exosome: a promising alternative in the therapy of Alzheimer’s disease. Alzheimers Res Ther. 2020;12:109.
51. Aguiar Koga BA, Fernandes LA, Fratini P, Sogayar MC, Carreira ACO. Role of MSC-derived small extracellular vesicles in tissue repair and regeneration. Front Cell Dev Biol. 2022;10:1047094.
52. Ma YN, Hu X, Karako K, Song P, Tang W, Xia Y. Exploring the multiple therapeutic mechanisms and challenges of mesenchymal stem cell-derived exosomes in Alzheimer’s disease. Biosci Trends. 2024;18:413-30.
53. Losurdo M, Pedrazzoli M, D’Agostino C, et al. Intranasal delivery of mesenchymal stem cell-derived extracellular vesicles exerts immunomodulatory and neuroprotective effects in a 3xTg model of Alzheimer’s disease. Stem Cells Transl Med. 2020;9:1068-84.
54. Liu X, Xia T, Fang Y, et al. Overcoming the blood-brain barrier by using a multistage exosome delivery system to inhibit central nervous system lymphoma. Nanomedicine. 2022;41:102523.
55. Song Y, Liang F, Tian W, Rayhill E, Ye L, Tian X. Optimizing therapeutic outcomes: preconditioning strategies for MSC-derived extracellular vesicles. Front Pharmacol. 2025;16:1509418.
56. Sha S, Shen X, Cao Y, Qu L. Mesenchymal stem cells-derived extracellular vesicles ameliorate Alzheimer’s disease in rat models via the microRNA-29c-3p/BACE1 axis and the Wnt/β-catenin pathway. Aging. 2021;13:15285-306.
57. Kaniowska D, Wenk K, Rademacher P, et al. Extracellular vesicles of mesenchymal stromal cells can be taken up by microglial cells and partially prevent the stimulation Induced by β-amyloid. Stem Cell Rev Rep. 2022;18:1113-26.
58. Ebrahim N, Al Saihati HA, Alali Z, et al. Exploring the molecular mechanisms of MSC-derived exosomes in Alzheimer’s disease: autophagy, insulin and the PI3K/Akt/mTOR signaling pathway. Biomed Pharmacother. 2024;176:116836.
59. Wang ZG, He ZY, Liang S, Yang Q, Cheng P, Chen AM. Comprehensive proteomic analysis of exosomes derived from human bone marrow, adipose tissue, and umbilical cord mesenchymal stem cells. Stem Cell Res Ther. 2020;11:511.
60. Shin S, Lee J, Kwon Y, et al. Comparative proteomic analysis of the mesenchymal stem cells secretome from adipose, bone marrow, placenta and Wharton’s jelly. Int J Mol Sci. 2021;22:845.
61. Fiandaca MS, Kapogiannis D, Mapstone M, et al. Identification of preclinical Alzheimer’s disease by a profile of pathogenic proteins in neurally derived blood exosomes: a case-control study. Alzheimers Dement. 2015;11:600-7.e1.
63. Brás IC, Khani MH, Riedel D, et al. Ectosomes and exosomes modulate neuronal spontaneous activity. J Proteomics. 2022;269:104721.
64. Kronman H, Singh A, Azam S, et al. Multidimensional effects of stress on neuronal exosome levels and simultaneous transcriptomic profiles. Biol Psychiatry Glob Open Sci. 2025;5:100401.
65. Murai Y, Honda T, Yuyama K, et al. Evaluation of plant ceramide species-induced exosome release from neuronal cells and exosome loading using deuterium chemistry. Int J Mol Sci. 2022;23:10751.
66. Nogueras-Ortiz CJ, Mahairaki V, Delgado-Peraza F, et al. Astrocyte- and neuron-derived extracellular vesicles from Alzheimer’s disease patients effect complement-mediated neurotoxicity. Cells. 2020;9:1618.
67. Winston CN, Aulston B, Rockenstein EM, et al. Neuronal exosome-derived human tau is toxic to recipient mouse neurons in vivo. J Alzheimers Dis. 2019;67:541-53.
68. Goetzl EJ, Mustapic M, Kapogiannis D, et al. Cargo proteins of plasma astrocyte-derived exosomes in Alzheimer’s disease. FASEB J. 2016;30:3853-9.
69. Xu H, Li H, Zhang P, et al. The functions of exosomes targeting astrocytes and astrocyte-derived exosomes targeting other cell types. Neural Regen Res. 2024;19:1947-53.
70. Söllvander S, Nikitidou E, Brolin R, et al. Accumulation of amyloid-β by astrocytes result in enlarged endosomes and microvesicle-induced apoptosis of neurons. Mol Neurodegener. 2016;11:38.
71. Gao S, Jia S, Bai L, Li D, Meng C. Transcriptome analysis unveils that exosomes derived from M1-polarized microglia induce ferroptosis of neuronal cells. Cells. 2022;11:3956.
72. Song Y, Li Z, He T, et al. M2 microglia-derived exosomes protect the mouse brain from ischemia-reperfusion injury via exosomal miR-124. Theranostics. 2019;9:2910-23.
73. Frühbeis C, Kuo-Elsner WP, Müller C, et al. Oligodendrocytes support axonal transport and maintenance via exosome secretion. PLoS Biol. 2020;18:e3000621.
74. Domingues HS, Falcão AM, Mendes-Pinto I, Salgado AJ, Teixeira FG. Exosome circuitry during (De)(Re)myelination of the central nervous system. Front Cell Dev Biol. 2020;8:483.
75. Du T, Yang CL, Ge MR, et al. M1 Macrophage derived exosomes aggravate experimental autoimmune neuritis via modulating Th1 response. Front Immunol. 2020;11:1603.
76. Qin J, Yuan H, An X, Liu R, Meng B. Macrophage-derived exosomes exacerbate postoperative cognitive dysfunction in mice through inflammation. J Neuroimmunol. 2024;394:578403.
77. Yuan D, Zhao Y, Banks WA, et al. Macrophage exosomes as natural nanocarriers for protein delivery to inflamed brain. Biomaterials. 2017;142:1-12.
78. Schey KL, Luther JM, Rose KL. Proteomics characterization of exosome cargo. Methods. 2015;87:75-82.
79. Arioz BI, Tufekci KU, Olcum M, et al. Proteome profiling of neuron-derived exosomes in Alzheimer’s disease reveals hemoglobin as a potential biomarker. Neurosci Lett. 2021;755:135914.
80. Song Z, Xu Y, Zhang L, et al. Comprehensive proteomic profiling of urinary exosomes and identification of potential non-invasive early biomarkers of Alzheimer’s disease in 5XFAD mouse model. Front Genet. 2020;11:565479.
81. Yuyama K, Sun H, Fujii R, Hemmi I, Ueda K, Igeta Y. Extracellular vesicle proteome unveils cathepsin B connection to Alzheimer’s disease pathogenesis. Brain. 2024;147:627-36.
82. Verma H, Dhureja M, Yadav A, et al. An in vivo C57BL/6 mouse study demonstrating fine-tuning of serum and brain-derived exosomes reveal therapeutic potential of phytochemical ferulic acid against Alzheimer’s disease. Mol Neurobiol. 2025;62:12963-83.
83. Liang Z, Zhuang H, Cao X, Ma G, Shen L. Subcellular proteomics insights into Alzheimer’s disease development. Proteomics Clin Appl. 2024;18:e2200112.
84. Cano A, Esteban-de-Antonio E, Bernuz M, et al. Plasma extracellular vesicles reveal early molecular differences in amyloid positive patients with early-onset mild cognitive impairment. J Nanobiotechnol. 2023;21:54.
85. Lee S, Jang KI, Lee H, et al. Multi-proteomic analyses of 5xFAD mice reveal new molecular signatures of early-stage Alzheimer’s disease. Aging Cell. 2024;23:e14137.
86. Jia L, Zhu M, Kong C, et al. Blood neuro-exosomal synaptic proteins predict Alzheimer’s disease at the asymptomatic stage. Alzheimers Dement. 2021;17:49-60.
87. Li Y, Xia M, Meng S, et al. MicroRNA-29c-3p in dual-labeled exosome is a potential diagnostic marker of subjective cognitive decline. Neurobiol Dis. 2022;171:105800.
88. Zhou X, Sheikh AM, Matsumoto KI, et al. iTRAQ-based proteomic analysis of APP transgenic mouse urine exosomes. Int J Mol Sci. 2022;24:672.
89. Soares Martins T, Marçalo R, da Cruz E Silva CB, et al. Novel exosome biomarker candidates for Alzheimer’s disease unravelled through mass spectrometry analysis. Mol Neurobiol. 2022;59:2838-54.
90. Park J, Lee J, Kim YS, Oh Y. Proteomic profiling of exosomes derived from endometrial stem cells and adipose-derived stem cells. Int J Stem Cells. 2026;19:102-12.
91. Liu Y, Zhang Z, Ma C, Song J, Hu J, Liu Y. Transplanted MSCs promote alveolar bone repair via hypoxia-induced extracellular vesicle secretion. Oral Dis. 2024;30:5221-31.
92. Podvin S, Jones A, Liu Q, et al. Mutant presenilin 1 dysregulates exosomal proteome cargo produced by human-induced pluripotent stem cell neurons. ACS Omega. 2021;6:13033-56.
93. Bhavsar PP, Kalita B, Taunk K, Rapole S. Decoding the key hallmarks of chemoresistance: a proteomic tale from breast cancer research. Biochim Biophys Acta Rev Cancer. 2025;1880:189404.
94. Woo HK, Ahn HS, Park J, et al. Size-dependent separation of extracellular vesicle subtypes with exodisc enabling proteomic analysis in prostate cancer. J Proteome Res. 2025;24:861-70.
95. Hakim MA, Sanni A, Osman ST, et al. Serum proteome profiling of diabetic patients treated with DPP4 and SGLT2 inhibitors shows improved cognitive and cardiovascular functions. Proteomics. 2025;25:e70000.
96. Zhang T, Ma S, Lv J, et al. The emerging role of exosomes in Alzheimer’s disease. Ageing Res Rev. 2021;68:101321.
97. Roach JC, Hara J, Fridman D, et al. The coaching for cognition in Alzheimer’s (COCOA) trial: study design. Alzheimers Dement (N Y). 2022;8:e12318.
98. Roach JC, Rapozo MK, Hara J, et al. ; COCOA Consortium:. A Remotely coached multimodal lifestyle intervention for Alzheimer’s disease ameliorates functional and cognitive outcomes. J Alzheimers Dis. 2023;96:591-607.
99. Liu S, Fan M, Xu JX, et al. Exosomes derived from bone-marrow mesenchymal stem cells alleviate cognitive decline in AD-like mice by improving BDNF-related neuropathology. J Neuroinflammation. 2022;19:35.
100. Cone AS, Yuan X, Sun L, et al. Mesenchymal stem cell-derived extracellular vesicles ameliorate Alzheimer’s disease-like phenotypes in a preclinical mouse model. Theranostics. 2021;11:8129-42.
101. Cui GH, Guo HD, Li H, et al. RVG-modified exosomes derived from mesenchymal stem cells rescue memory deficits by regulating inflammatory responses in a mouse model of Alzheimer’s disease. Immun Ageing. 2019;16:10.
102. Chen C, Bao Y, Xing L, et al. Exosomes derived from M2 microglial cells modulated by 1070-nm light improve cognition in an Alzheimer’s disease mouse model. Adv Sci (Weinh). 2023;10:e2304025.
103. Zhu L, Zhou T, Wu L, et al. Microglial exosome TREM2 ameliorates ferroptosis and neuroinflammation in Alzheimer’s disease by activating the Wnt/β-catenin signaling. Sci Rep. 2025;15:24968.
104. Xu X, Li J, Wang F, et al. Genetic and pathway complexity in Alzheimer’s disease: Insights from multi-omic data about the immune response and mitochondrial function. Neural Regen Res. 2025;Epub ahead of print.
105. Wang C, Cui C, Xu P, et al. Targeting PDK2 rescues stress-induced impaired brain energy metabolism. Mol Psychiatry. 2023;28:4138-50.
106. Li H, Sun J, Wu Y, Yang Y, Zhang W, Tian Y. Honokiol relieves hippocampal neuronal damage in Alzheimer’s disease by activating the SIRT3-mediated mitochondrial autophagy. CNS Neurosci Ther. 2024;30:e14878.
107. Reid DM, Barber RC, Thorpe RJ Jr, Sun J, Zhou Z, Phillips NR. Mitochondrial DNA oxidative mutations are elevated in Mexican American women potentially implicating Alzheimer’s disease. NPJ Aging. 2022;8:2.
108. Wang Z, Wang C, Yuan B, et al. Akkermansia muciniphila and its metabolite propionic acid maintains neuronal mitochondrial division and autophagy homeostasis during Alzheimer’s disease pathologic process via GPR41 and GPR43. Microbiome. 2025;13:16.
109. Zhang W, Hong J, Zhang H, Zheng W, Yang Y. Astrocyte-derived exosomes protect hippocampal neurons after traumatic brain injury by suppressing mitochondrial oxidative stress and apoptosis. Aging. 2021;13:21642-58.
110. Jung YH, Jo HY, Kim DH, et al. Exosome-mediated mitochondrial regulation: a promising therapeutic tool for Alzheimer’s disease and Parkinson’s disease. Int J Nanomedicine. 2025;20:4903-17.
111. Ding YN, Li MQ, Song JY, Guan PP, Wang P. Engineered exosomes improve the effects of curcumin on protecting mitochondria of neurons in Alzheimer’s disease. Mater Today Bio. 2025;32:101738.
112. Fairley LH, Lai KO, Wong JH, et al. Mitochondrial control of microglial phagocytosis by the translocator protein and hexokinase 2 in Alzheimer’s disease. Proc Natl Acad Sci U S A. 2023;120:e2209177120.
113. Asiamah EA, Feng B, Guo R, et al. The contributions of the endolysosomal compartment and autophagy to APOEɛ4 allele-mediated increase in Alzheimer’s disease risk. J Alzheimers Dis. 2024;97:1007-31.
114. Nakashima M, Suga N, Fukumoto A, Yoshikawa S, Matsuda S. Exosomes, endosomes, and caveolae as encouraging targets with favorable gut microbiota for the innovative treatment of Alzheimer’s diseases. Discov Med. 2024;36:2132-42.
115. Liu P, Wu A, Li H, et al. Rab21 protein is degraded by both the ubiquitin-proteasome pathway and the autophagy-lysosome pathway. Int J Mol Sci. 2022;23:1131.
116. Qian J, Ren S, Ren T, Shi R, Qiao L, Kang J. Astrocyte autophagy in neurodegenerative diseases: current progress in mechanisms and therapeutics. Neurochem Res. 2025;50:287.
117. Lin J, Yuan Y, Huang C, et al. TFEB agonist clomiphene citrate activates the autophagy-lysosomal pathway and ameliorates Alzheimer’s disease symptoms in mice. J Biol Chem. 2024;300:107929.
118. Rai SN, Tiwari N, Singh P, et al. Therapeutic potential of vital transcription factors in Alzheimer’s and Parkinson’s disease with particular emphasis on transcription factor EB mediated autophagy. Front Neurosci. 2021;15:777347.
119. Liu H, Li C, Zhang X, et al. BMSC-Exosomes attenuate ALP dysfunction by restoring lysosomal function via the mTOR/TFEB Axis to reduce cerebral ischemia-reperfusion injury. Exp Neurol. 2024;376:114726.
120. Zhang S, Qiu Y, Feng Y, et al. Calpain-2 facilitates autophagic/lysosomal defects and apoptosis in ARPE-19 cells and rats induced by exosomes from RPE cells under NaIO3 stimulation. Oxid Med Cell Longev. 2023;2023:3310621.
121. Cazzaro S, Fang C, Khan H, et al. Slingshot homolog-1 mediates the secretion of small extracellular vesicles containing misfolded proteins by regulating autophagy cargo receptors and actin dynamics. Front Aging Neurosci. 2022;14:933979.
122. Kim SJ, Russell AE, Wang W, et al. miR-146a Dysregulates energy metabolism during neuroinflammation. J Neuroimmune Pharmacol. 2022;17:228-41.
123. Han J, Zhang X, Kang L, Guan J. Extracellular vesicles as therapeutic modulators of neuroinflammation in Alzheimer’s disease: a focus on signaling mechanisms. J Neuroinflammation. 2025;22:120.
124. Xie HM, Su X, Zhang FY, et al. Profile of the RNA in exosomes from astrocytes and microglia using deep sequencing: implications for neurodegeneration mechanisms. Neural Regen Res. 2022;17:608-17.
125. Ye Y, Gao M, Shi W, et al. The immunomodulatory effects of mesenchymal stem cell-derived extracellular vesicles in Alzheimer’s disease. Front Immunol. 2023;14:1325530.
126. Park AM, Tsunoda I. Helicobacter pylori infection in the stomach induces neuroinflammation: the potential roles of bacterial outer membrane vesicles in an animal model of Alzheimer’s disease. Inflamm Regen. 2022;42:39.
127. Liu WL, Lin HW, Lin MR, et al. Emerging blood exosome-based biomarkers for preclinical and clinical Alzheimer’s disease: a meta-analysis and systematic review. Neural Regen Res. 2022;17:2381-90.
128. Kalluri VS, Smaglo BG, Mahadevan KK, et al. Engineered exosomes with Kras(G12D) specific siRNA in pancreatic cancer: a phase I study with immunological correlates. Nat Commun. 2025;16:8696.
129. Li M, Huang H, Wei X, et al. Correction: clinical investigation on nebulized human umbilical cord MSC-derived extracellular vesicles for pulmonary fibrosis treatment. Signal Transduct Target Ther. 2025;10:235.
130. Xie X, Song Q, Dai C, et al. Clinical safety and efficacy of allogenic human adipose mesenchymal stromal cells-derived exosomes in patients with mild to moderate Alzheimer’s disease: a phase I/II clinical trial. Gen Psychiatr. 2023;36:e101143.
131. Ramon J, Pinheiro C, Vandendriessche C, et al. Pre-formation loading of extracellular vesicles with exogenous molecules using photoporation. J Nanobiotechnol. 2025;23:556.
132. Obuchi W, Zargani-Piccardi A, Leandro K, et al. Engineering of CD63 enables selective extracellular vesicle cargo loading and enhanced payload delivery. J Extracell Vesicles. 2025;14:e70094.
133. Huang K, Garimella S, Clay-Gilmour A, et al. Comparison of human urinary exosomes isolated via ultracentrifugation alone versus ultracentrifugation followed by SEC Column-purification. J Pers Med. 2022;12:340.
134. Kluszczyńska K, Pęczek Ł, Różański A, Czernek L, Duechler M. U6/miR-211 expression ratio as a purity parameter for HEK293 cell-derived exosomes. Acta Biochim Pol. 2022;69:409-15.
135. Jiang Z, Liu G, Li J. Recent progress on the isolation and detection methods of exosomes. Chem Asian J. 2020;15:3973-82.
136. Zarovni N, Corrado A, Guazzi P, et al. Integrated isolation and quantitative analysis of exosome shuttled proteins and nucleic acids using immunocapture approaches. Methods. 2015;87:46-58.
137. An M, Wu J, Zhu J, Lubman DM. Comparison of an optimized ultracentrifugation method versus size-exclusion chromatography for isolation of exosomes from human serum. J Proteome Res. 2018;17:3599-605.
138. Sidhom K, Obi PO, Saleem A. A review of exosomal isolation methods: is size exclusion chromatography the best option? Int J Mol Sci. 2020;21:6466.
139. Brown PN, Yin H. Polymer-based purification of extracellular vesicles. Methods Mol Biol. 2017;1660:91-103.
140. Huang LH, Rau CS, Wu SC, et al. Identification and characterization of hADSC-derived exosome proteins from different isolation methods. J Cell Mol Med. 2021;25:7436-50.
141. Kurian TK, Banik S, Gopal D, Chakrabarti S, Mazumder N. Elucidating methods for isolation and quantification of exosomes: a review. Mol Biotechnol. 2021;63:249-66.
142. Abaidullah N, Muhammad K, Waheed Y. Delving into nanoparticle systems for enhanced drug delivery technologies. AAPS PharmSciTech. 2025;26:74.
143. Zhou C, Zhang B, Yang Y, et al. Stem cell-derived exosomes: emerging therapeutic opportunities for wound healing. Stem Cell Res Ther. 2023;14:107.
144. Dairov A, Issabekova A, Sarsenova M, et al. Study of the Therapeutic effect of cytokine-preconditioned mesenchymal stem cells and their exosomes in a mouse model of psoriasis. Biology (Basel). 2025;14:1033.
145. Kwon HH, Yang SH, Lee J, et al. Combination treatment with human adipose tissue stem cell-derived exosomes and fractional CO2 laser for acne scars: a 12-week prospective, double-blind, randomized, split-face study. Acta Derm Venereol. 2020;100:adv00310.
146. Catitti G, Cufaro MC, De Bellis D, et al. Extracellular vesicles in regenerative processes associated with muscle injury recovery of professional athletes undergoing sub maximal strength rehabilitation. Int J Mol Sci. 2022;23:14913.
147. Bu Z, Jing J, Liu W, et al. Treatment of denervated muscle atrophy by injectable dual-responsive hydrogels loaded with extracellular vesicles. Adv Sci (Weinh). 2025;12:e2412248.
148. Lu X, Xu R, Dong X, et al. Cell-derived exosome therapy for diabetic peripheral neuropathy: a preclinical animal studies systematic review and meta-analysis. Stem Cell Res Ther. 2025;16:297.
149. Lee JY, Kim J, Na K, Ahn HJ. GMP manufacturing of umbilical cord blood mesenchymal stem cell-released exosomes and verification of wound healing efficacy. Nanotheranostics. 2025;9:95-109.
151. Li J, Lee Y, Johansson HJ, et al. Serum-free culture alters the quantity and protein composition of neuroblastoma-derived extracellular vesicles. J Extracell Vesicles. 2015;4:26883.
152. Duan L, Li X, Xu X, et al. Large-scale preparation of synovial fluid mesenchymal stem cell-derived exosomes by 3D bioreactor culture. J Vis Exp. 2022.
153. Lin B, Lei Y, Wang J, et al. Microfluidic-based exosome analysis for liquid biopsy. Small Methods. 2021;5:e2001131.
154. Zhang W, Lu R, Zhang L. Preparation of dual-functional composite magnetic nanomaterials modified with different metals/aptamers and their performance in exosome enrichment. Se Pu. 2021;39:1128-36.
155. Lee JH, Ha DH, Go HK, et al. Reproducible large-scale isolation of exosomes from adipose tissue-derived mesenchymal stem/stromal cells and their application in acute kidney injury. Int J Mol Sci. 2020;21:4774.
156. Ulpiano C, Salvador W, Franchi-Mendes T, et al. Continuous collection of human mesenchymal-stromal-cell-derived extracellular vesicles from a stirred tank reactor operated under xenogeneic-free conditions for therapeutic applications. Stem Cell Res Ther. 2025;16:210.
157. Ma CY, Zhai Y, Li CT, et al. Translating mesenchymal stem cell and their exosome research into GMP compliant advanced therapy products: promises, problems and prospects. Med Res Rev. 2024;44:919-38.
158. Shahlaei M, Afkhami H, Ahmadieh-Yazdi A, et al. Corrigendum to “Exosomes in Alzheimer’s disease: from pathogenesis to therapeutics - a comprehensive review of diagnostic and drug delivery applications” [Biomed. Pharmacother. 192 (2025) 118548]. Biomed Pharmacother. 2025;192:118632.
159. Ebadpour N, Abavisani M, Karav S, Kesharwani P, Sahebkar A. Exosome/Extracellular vesicles-based therapeutics in Alzheimer’s disease: neuroprotective roles and future perspectives. J Mol Neurosci. 2025;75:137.
160. Chen YS, Lin EY, Chiou TW, Harn HJ. Exosomes in clinical trial and their production in compliance with good manufacturing practice. Tzu Chi Med J. 2020;32:113-20.
161. Gurriaran-Rodriguez U, De Repentigny Y, Kothary R, Rudnicki MA. Isolation of small extracellular vesicles from regenerating muscle tissue using tangential flow filtration and size exclusion chromatography. Skelet Muscle. 2024;14:22.
162. Gelibter S, Marostica G, Mandelli A, et al. The impact of storage on extracellular vesicles: A systematic study. J Extracell Vesicles. 2022;11:e12162.
163. Lu L, Han C, Wang M, et al. Assessment of bovine milk exosome preparation and lyophilized powder stability. J Extracell Biol. 2024;3:e70009.
164. Budgude P, Kale V, Vaidya A. Cryopreservation of mesenchymal stromal cell-derived extracellular vesicles using trehalose maintains their ability to expand hematopoietic stem cells in vitro. Cryobiology. 2021;98:152-63.
165. Wang CK, Tsai TH, Lee CH. Regulation of exosomes as biologic medicines: Regulatory challenges faced in exosome development and manufacturing processes. Clin Transl Sci. 2024;17:e13904.
166. Huang Q, Wang S, Liu Z, Rao L, Cheng K, Mao X. Engineering exosomes for targeted neurodegenerative therapy: innovations in biogenesis, drug loading, and clinical translation. Theranostics. 2026;16:545-79.
167. Li Q, Li Y, Shao J, et al. Exploring regulatory frameworks for exosome therapy: insights and perspectives. Health Care Sci. 2025;4:299-309.
168. Ansarian MA, Fatahichegeni M, Wang Y, Ren J, Zhang T, Wang X. Exosomal biomarkers in leukemia: translational potential and regulatory challenges for precision medicine applications. Front Immunol. 2025;16:1677088.
169. Azuma K, Yamanaka S. Recent policies that support clinical application of induced pluripotent stem cell-based regenerative therapies. Regen Ther. 2016;4:36-47.
170. Sanborn V, Drake JD, Alaimo H, et al. Investigating salivary extracellular vesicles as biomarkers for Alzheimer’s disease: ExosomeAD study design and baseline characteristics. Alzheimers Dement. 2026;21 Suppl:e105183.
171. Van Delen M, Derdelinckx J, Wouters K, Nelissen I, Cools N. A systematic review and meta-analysis of clinical trials assessing safety and efficacy of human extracellular vesicle-based therapy. J Extracell Vesicles. 2024;13:e12458.
172. Yang Y, Wang F, Li Y, et al. Engineered extracellular vesicles with polypeptide for targeted delivery of doxorubicin against EGFR‑positive tumors. Oncol Rep. 2024;52:154.
173. Sun D, Zhuang X, Xiang X, et al. A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes. Mol Ther. 2010;18:1606-14.
174. Gong L, Chen Z, Feng K, et al. A versatile engineered extracellular vesicle platform simultaneously targeting and eliminating senescent stromal cells and tumor cells to promote tumor regression. J Nanobiotechnol. 2024;22:105.
175. Kim HK, Choi Y, Kim KH, et al. Scalable production of siRNA-encapsulated extracellular vesicles for the inhibition of KRAS-mutant cancer using acoustic shock waves. J Extracell Vesicles. 2024;13:e12508.
176. Pham TC, Jayasinghe MK, Pham TT, et al. Covalent conjugation of extracellular vesicles with peptides and nanobodies for targeted therapeutic delivery. J Extracell Vesicles. 2021;10:e12057.
177. Gu Y, Li A, Zeng Y, et al. Engineering hybrid nanoparticles for targeted codelivery of triptolide and CYP3A4-siRNA against pulmonary metastatic melanoma. Sci Adv. 2025;11:eadv6990.
178. Zhu Z, Zhai Y, Hao Y, et al. Specific anti-glioma targeted-delivery strategy of engineered small extracellular vesicles dual-functionalised by Angiopep-2 and TAT peptides. J Extracell Vesicles. 2022;11:e12255.
179. Li B, Chen X, Qiu W, et al. Synchronous disintegration of ferroptosis defense axis via engineered exosome-conjugated magnetic nanoparticles for glioblastoma therapy. Adv Sci (Weinh). 2022;9:e2105451.
180. Zhang H, Feng K, Han M, et al. Homologous magnetic targeted immune vesicles for amplifying immunotherapy via ferroptosis activation augmented photodynamic therapy against glioblastoma. J Control Release. 2025;383:113816.
181. Lin EY, Hsu SX, Wu BH, et al. Engineered exosomes containing microRNA-29b-2 and targeting the somatostatin receptor reduce presenilin 1 expression and decrease the β-amyloid accumulation in the brains of mice with Alzheimer’s disease. Int J Nanomedicine. 2024;19:4977-94.
182. Wang Y, Huo Y, Zhao C, et al. Engineered exosomes with enhanced stability and delivery efficiency for glioblastoma therapy. J Control Release. 2024;368:170-83.
183. Yang J, Li Y, Jiang S, et al. Engineered brain-targeting exosome for reprogramming immunosuppressive microenvironment of glioblastoma. Exploration (Beijing). 2025;5:20240039.
184. Hua D, Tang L, Wang W, et al. Improved antiglioblastoma activity and BBB permeability by conjugation of paclitaxel to a cell-penetrative MMP-2-cleavable peptide. Adv Sci (Weinh). 2021;8:2001960.
185. Ma M, Wang J, Zhong W, Li Z, Zhao Y. Cleavable antibody-conjugated Aβ specific immune exosome for combination Alzheimer’s disease immunotherapy. Angew Chem Int Ed Engl. 2025;64:e202517917.
186. Li M, Lu L, Bao Q, et al. Radiotherapy-derived engineered stem cell exosomes improve anti-glioma immunotherapy by promoting the formation of tertiary lymphoid structure and improve the release of type I interferon. J Nanobiotechnol. 2025;23:239.
187. Tian T, Liang R, Erel-Akbaba G, et al. Immune checkpoint inhibition in GBM primed with radiation by engineered extracellular vesicles. ACS Nano. 2022;16:1940-53.
188. Dong Z, Yin T, Deng Z, et al. Hybridoma-inspired strategy crafts tailored multifunctional exosomes for precision therapy. Proc Natl Acad Sci U S A. 2025;122:e2424547122.
189. Du B, Zou Q, Wang X, et al. Multi-targeted engineered hybrid exosomes as Aβ nanoscavengers and inflammatory modulators for multi-pathway intervention in Alzheimer’s disease. Biomaterials. 2025;322:123403.
190. Han J, Sul JH, Lee J, et al. Engineered exosomes with a photoinducible protein delivery system enable CRISPR-Cas-based epigenome editing in Alzheimer’s disease. Sci Transl Med. 2024;16:eadi4830.
191. Liu H, Jin M, Ji M, Zhang W, Liu A, Wang T. Hypoxic pretreatment of adipose-derived stem cell exosomes improved cognition by delivery of circ-Epc1 and shifting microglial M1/M2 polarization in an Alzheimer’s disease mice model. Aging. 2022;14:3070-83.
192. Huber CC, Callegari EA, Paez MD, Romanova S, Wang H. Heat shock-induced extracellular vesicles derived from neural stem cells confer marked neuroprotection against oxidative stress and amyloid-β-caused neurotoxicity. Mol Neurobiol. 2022;59:7404-12.
193. Xu Y, Dong Y, Wang C, Jiang Q, Chu H, Tian Y. Lovastatin attenuates sevoflurane-induced cognitive disorder in aged rats via reducing Aβ accumulation. Neurochem Int. 2021;148:105078.
194. Liang J, Zhao J, Yang L, et al. MSC-exosomes pretreated by Danshensu extracts pretreating to target the hsa-miR-27a-5p and STAT3-SHANK2 to enhanced antifibrotic therapy. Stem Cell Res Ther. 2025;16:40.
195. Chen L, Zhang J, Yu J, Guo S, Tian W. LPS pretreated dental follicle stem cell derived exosomes promote periodontal tissue regeneration via miR-184 and PPARα-Akt-JNK signaling pathway. Stem Cell Res Ther. 2025;16:347.
196. Olson C, Ivanov K, Boyes D, et al. Dual-omics approach unveils novel perspective on the quality control of genetically engineered exosomes. Pharmaceutics. 2024;16:824.
