REFERENCES
1. Andaloussi S, Mäger I, Breakefield XO, Wood MJ. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov 2013;12:347-57.
2. Mathieu M, Martin-Jaular L, Lavieu G, Théry C. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol 2019;21:9-17.
3. Rädler J, Gupta D, Zickler A, Andaloussi SE. Exploiting the biogenesis of extracellular vesicles for bioengineering and therapeutic cargo loading. Mol Ther 2023;31:1231-50.
4. Jeppesen DK, Zhang Q, Franklin JL, Coffey RJ. Extracellular vesicles and nanoparticles: emerging complexities. Trends Cell Biol 2023;33:667-81.
5. Zhang X, Zhang H, Gu J, et al. Engineered extracellular vesicles for cancer therapy. Adv Mater 2021;33:e2005709.
6. Munagala R, Aqil F, Jeyabalan J, Gupta RC. Bovine milk-derived exosomes for drug delivery. Cancer Lett 2016;371:48-61.
7. Jeppesen DK, Fenix AM, Franklin JL, et al. Reassessment of exosome composition. Cell 2019;177:428-445.e18.
8. Buzas EI. The roles of extracellular vesicles in the immune system. Nat Rev Immunol 2023;23:236-50.
9. Raposo G, Stahl PD. Extracellular vesicles - on the cusp of a new language in the biological sciences. Extracell Vesicles Circ Nucleic Acids 2023;4:240-54.
10. Dooley K, McConnell RE, Xu K, et al. A versatile platform for generating engineered extracellular vesicles with defined therapeutic properties. Mol Ther 2021;29:1729-43.
11. Liang Y, Duan L, Lu J, Xia J. Engineering exosomes for targeted drug delivery. Theranostics 2021;11:3183-95.
12. Harding C, Heuser J, Stahl P. Endocytosis and intracellular processing of transferrin and colloidal gold-transferrin in rat reticulocytes: demonstration of a pathway for receptor shedding. Eur J Cell Biol 1984;35:256-63.
13. Buzas EI, György B, Nagy G, Falus A, Gay S. Emerging role of extracellular vesicles in inflammatory diseases. Nat Rev Rheumatol 2014;10:356-64.
14. 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.
15. Yang B, Chen Y, Shi J. Exosome biochemistry and advanced nanotechnology for next-generation theranostic platforms. Adv Mater 2019;31:e1802896.
16. Gurunathan S, Kang MH, Jeyaraj M, Qasim M, Kim JH. Review of the isolation, characterization, biological function, and multifarious therapeutic approaches of exosomes. Cells 2019;8:307.
17. Tauro BJ, Greening DW, Mathias RA, et al. Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes. Methods 2012;56:293-304.
18. Linares R, Tan S, Gounou C, Arraud N, Brisson AR. High-speed centrifugation induces aggregation of extracellular vesicles. J Extracell Vesicles 2015;4:29509.
19. Van Deun J, Mestdagh P, Sormunen R, et al. The impact of disparate isolation methods for extracellular vesicles on downstream RNA profiling. J Extracell Vesicles 2014:3.
20. Mol EA, Goumans MJ, Doevendans PA, Sluijter JPG, Vader P. Higher functionality of extracellular vesicles isolated using size-exclusion chromatography compared to ultracentrifugation. Nanomedicine 2017;13:2061-5.
21. Contreras-Naranjo JC, Wu HJ, Ugaz VM. Microfluidics for exosome isolation and analysis: enabling liquid biopsy for personalized medicine. Lab Chip 2017;17:3558-77.
22. Cheng Q, Kang Y, Yao B, et al. Genetically engineered-cell-membrane nanovesicles for cancer immunotherapy. Adv Sci 2023;10:e2302131.
23. Jang SC, Kim OY, Yoon CM, et al. Bioinspired exosome-mimetic nanovesicles for targeted delivery of chemotherapeutics to malignant tumors. ACS Nano 2013;7:7698-710.
24. Fuhrmann G, Serio A, Mazo M, Nair R, Stevens MM. Active loading into extracellular vesicles significantly improves the cellular uptake and photodynamic effect of porphyrins. J Control Release 2015;205:35-44.
25. Haney MJ, Klyachko NL, Zhao Y, et al. Exosomes as drug delivery vehicles for Parkinson's disease therapy. J Control Release 2015;207:18-30.
26. Jhan YY, Prasca-Chamorro D, Palou Zuniga G, et al. Engineered extracellular vesicles with synthetic lipids via membrane fusion to establish efficient gene delivery. Int J Pharm 2020;573:118802.
27. Wen Y, Fu Q, Soliwoda A, et al. Cell-derived nanovesicles prepared by membrane extrusion are good substitutes for natural extracellular vesicles. Extracell Vesicle 2022;1:100004.
28. Li J, Sharkey CC, Wun B, Liesveld JL, King MR. Genetic engineering of platelets to neutralize circulating tumor cells. J Control Release 2016;228:38-47.
29. Lewis ND, Sia CL, Kirwin K, et al. Exosome surface display of IL12 results in tumor-retained pharmacology with superior potency and limited systemic exposure compared with recombinant IL12. Mol Cancer Ther 2021;20:523-34.
30. Wu WC, Tian J, Xiao D, et al. Engineered extracellular vesicles encapsulated Bryostatin-1 as therapy for neuroinflammation. Nanoscale 2022;14:2393-410.
31. Xu F, Wu Y, Yang Q, et al. Engineered extracellular vesicles with SHP2 high expression promote mitophagy for alzheimer's disease treatment. Adv Mater 2022;34:e2207107.
32. Lv P, Liu X, Chen X, et al. Genetically engineered cell membrane nanovesicles for oncolytic adenovirus delivery: a versatile platform for cancer virotherapy. Nano Lett 2019;19:2993-3001.
33. Zhang P, Zhang L, Qin Z, et al. Genetically engineered liposome-like nanovesicles as active targeted transport platform. Adv Mater 2018;30:1705350.
34. Liu C, Liu X, Xiang X, et al. A nanovaccine for antigen self-presentation and immunosuppression reversal as a personalized cancer immunotherapy strategy. Nat Nanotechnol 2022;17:531-40.
35. Komuro H, Aminova S, Lauro K, Harada M. Advances of engineered extracellular vesicles-based therapeutics strategy. Sci Technol Adv Mater 2022;23:655-81.
36. Cheng Q, Shi X, Han M, Smbatyan G, Lenz HJ, Zhang Y. Reprogramming exosomes as nanoscale controllers of cellular immunity. J Am Chem Soc 2018;140:16413-7.
37. Cheng Q, Dai Z, Smbatyan G, Epstein AL, Lenz HJ, Zhang Y. Eliciting anti-cancer immunity by genetically engineered multifunctional exosomes. Mol Ther 2022;30:3066-77.
38. Xue T, Zhang Z, Fang T, et al. Cellular vesicles expressing PD-1-blocking scFv reinvigorate T cell immunity against cancer. Nano Res 2022;15:5295-5304.
40. Tian Y, Li S, Song J, et al. A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Biomaterials 2014;35:2383-90.
41. Zhou Y, Yuan Y, Liu M, Hu X, Quan Y, Chen X. Tumor-specific delivery of KRAS siRNA with iRGD-exosomes efficiently inhibits tumor growth. ExRNA 2019;1:28.
42. Zhu Q, Ling X, Yang Y, et al. Embryonic stem cells-derived exosomes endowed with targeting properties as chemotherapeutics delivery vehicles for glioblastoma therapy. Adv Sci 2019;6:1801899.
43. Tao SC, Li XR, Wei WJ, et al. Polymeric coating on β-TCP scaffolds provides immobilization of small extracellular vesicles with surface-functionalization and ZEB1-Loading for bone defect repair in diabetes mellitus. Biomaterials 2022;283:121465.
44. Kim MS, Haney MJ, Zhao Y, et al. Engineering macrophage-derived exosomes for targeted paclitaxel delivery to pulmonary metastases: in vitro and in vivo evaluations. Nanomedicine 2018;14:195-204.
45. Jang SC, Economides KD, Moniz RJ, et al. ExoSTING, an extracellular vesicle loaded with STING agonists, promotes tumor immune surveillance. Commun Biol 2021;4:497.
46. Huang CC, Kang M, Lu Y, et al. Functionally engineered extracellular vesicles improve bone regeneration. Acta Biomater 2020;109:182-94.
47. Song Y, Li M, Lei S, et al. Silk sericin patches delivering miRNA-29-enriched extracellular vesicles-decorated myoblasts (SPEED) enhances regeneration and functional repair after severe skeletal muscle injury. Biomaterials 2022;287:121630.
48. McAndrews KM, Xiao F, Chronopoulos A, LeBleu VS, Kugeratski FG, Kalluri R. Exosome-mediated delivery of CRISPR/Cas9 for targeting of oncogenic Kras(G12D) in pancreatic cancer. Life Sci Alliance 2021;4:e202000875.
49. Gee P, Lung MSY, Okuzaki Y, et al. Extracellular nanovesicles for packaging of CRISPR-Cas9 protein and sgRNA to induce therapeutic exon skipping. Nat Commun 2020;11:1334.
50. Yao X, Lyu P, Yoo K, et al. Engineered extracellular vesicles as versatile ribonucleoprotein delivery vehicles for efficient and safe CRISPR genome editing. J Extracell Vesicles 2021;10:e12076.
51. Bai J, Duan J, Liu R, et al. Engineered targeting tLyp-1 exosomes as gene therapy vectors for efficient delivery of siRNA into lung cancer cells. Asian J Pharm Sci 2020;15:461-71.
52. Bellavia D, Raimondo S, Calabrese G, et al. Interleukin 3- receptor targeted exosomes inhibit in vitro and in vivo chronic myelogenous leukemia cell growth. Theranostics 2017;7:1333-45.
53. Lu M, Xing H, Shao W, et al. Photoactivatable silencing extracellular vesicle (pasev) sensitizes cancer immunotherapy. Adv Mater 2022;34:e2204765.
54. Wu S, Zhang J, Pan J, et al. Integrated nanorod-mediated PD-L1 downregulation in combination with oxidative-stress immunogene therapy against cancer. Adv Healthc Mater 2023;12:e2300110.
55. Haltom AR, Hassen WE, Hensel J, et al. Engineered exosomes targeting MYC reverse the proneural-mesenchymal transition and extend survival of glioblastoma. Extracell Vesicle 2022;1:100014.
56. Sun Q, Hong Z, Zhang C, Wang L, Han Z, Ma D. Immune checkpoint therapy for solid tumours: clinical dilemmas and future trends. Signal Transduct Target Ther 2023;8:320.
57. Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J 1992;11:3887-95.
58. Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 2000;192:1027-34.
59. Latchman Y, Wood CR, Chernova T, et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol 2001;2:261-8.
60. Kornepati AVR, Vadlamudi RK, Curiel TJ. Programmed death ligand 1 signals in cancer cells. Nat Rev Cancer 2022;22:174-89.
61. Li B, Fang T, Li Y, et al. Engineered T cell extracellular vesicles displaying PD-1 boost anti-tumor immunity. Nano Today 2022;46:101606.
62. Zhang X, Wang C, Wang J, et al. PD-1 blockade cellular vesicles for cancer immunotherapy. Adv Mater 2018;30:e1707112.
63. Xu F, Jiang D, Xu J, et al. Engineering of dendritic cell bispecific extracellular vesicles for tumor-targeting immunotherapy. Cell Rep 2023;42:113138.
64. Li L, Miao Q, Meng F, et al. Genetic engineering cellular vesicles expressing CD64 as checkpoint antibody carrier for cancer immunotherapy. Theranostics 2021;11:6033-43.
65. Fang W, Li L, Lin Z, et al. Engineered IL-15/IL-15R α -expressing cellular vesicles promote T cell anti-tumor immunity. Extracell Vesicles 2023;2:100021.
66. 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.
67. Kuderer NM, Desai A, Lustberg MB, Lyman GH. Mitigating acute chemotherapy-associated adverse events in patients with cancer. Nat Rev Clin Oncol 2022;19:681-97.
68. Keklikoglou I, Cianciaruso C, Güç E, et al. Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models. Nat Cell Biol 2019;21:190-202.
69. Wills CA, Liu X, Chen L, et al. Chemotherapy-induced upregulation of small extracellular vesicle-associated PTX3 accelerates breast cancer metastasis. Cancer Res 2021;81:452-63.
70. Voloshin T, Alishekevitz D, Kaneti L, et al. Blocking IL1β pathway following paclitaxel chemotherapy slightly inhibits primary tumor growth but promotes spontaneous metastasis. Mol Cancer Ther 2015;14:1385-94.
71. Liu G, Chen Y, Qi F, et al. Specific chemotherapeutic agents induce metastatic behaviour through stromal- and tumour-derived cytokine and angiogenic factor signalling. J Pathol 2015;237:190-202.
72. Zhang Z, Yao S, Hu Y, Zhao X, Lee RJ. Application of lipid-based nanoparticles in cancer immunotherapy. Front Immunol 2022;13:967505.
73. Liu X, Zhang G, Yu T, et al. CL4-modified exosomes deliver lncRNA DARS-AS1 siRNA to suppress triple-negative breast cancer progression and attenuate doxorubicin resistance by inhibiting autophagy. Int J Biol Macromol 2023;250:126147.
74. Zhou W, Zhou Y, Chen X, et al. Pancreatic cancer-targeting exosomes for enhancing immunotherapy and reprogramming tumor microenvironment. Biomaterials 2021;268:120546.
75. Jaffray DA, Knaul F, Baumann M, Gospodarowicz M. Harnessing progress in radiotherapy for global cancer control. Nat Cancer 2023;4:1228-38.
76. Wan FZ, Chen KH, Sun YC, et al. Exosomes overexpressing miR-34c inhibit malignant behavior and reverse the radioresistance of nasopharyngeal carcinoma. J Transl Med 2020;18:12.
77. Jiang J, Tang Q, Gong J, et al. Radiosensitizer EXO-miR-197-3p inhibits nasopharyngeal carcinoma progression and radioresistance by regulating the AKT/mTOR axis and HSPA5-mediated autophagy. Int J Biol Sci 2022;18:1878-95.
78. Kamerkar S, LeBleu VS, Sugimoto H, et al. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature 2017;546:498-503.
80. Fugger L, Jensen LT, Rossjohn J. Challenges, progress, and prospects of developing therapies to treat autoimmune diseases. Cell 2020;181:63-80.
81. Foulis AK, McGill M, Farquharson MA. Insulitis in type 1 (insulin-dependent) diabetes mellitus in man--macrophages, lymphocytes, and interferon-gamma containing cells. J Pathol 1991;165:97-103.
82. Katsarou A, Gudbjörnsdottir S, Rawshani A, et al. Type 1 diabetes mellitus. Nat Rev Dis Primers 2017;3:17016.
83. Zhang X, Kang Y, Wang J, et al. Engineered PD-L1-expressing platelets reverse new-onset type 1 diabetes. Adv Mater 2020;32:1907692.
84. Becker MW, Peters LD, Myint T, et al. Immune engineered extracellular vesicles to modulate T cell activation in the context of type 1 diabetes. Sci Adv 2023;9:eadg1082.
85. Ying W, Riopel M, Bandyopadhyay G, et al. Adipose tissue macrophage-derived exosomal miRNAs can modulate in vivo and in vitro insulin sensitivity. Cell 2017;171:372-84.e12.
86. Deng ZB, Poliakov A, Hardy RW, et al. Adipose tissue exosome-like vesicles mediate activation of macrophage-induced insulin resistance. Diabetes 2009;58:2498-505.
87. Ying W, Gao H, Dos Reis FCG, et al. MiR-690, an exosomal-derived miRNA from M2-polarized macrophages, improves insulin sensitivity in obese mice. Cell Metab 2021;33:781-790.e5.
88. Ferrante SC, Nadler EP, Pillai DK, et al. Adipocyte-derived exosomal miRNAs: a novel mechanism for obesity-related disease. Pediatr Res 2015;77:447-54.
89. Li C, Ni YQ, Xu H, et al. Roles and mechanisms of exosomal non-coding RNAs in human health and diseases. Signal Transduct Target Ther 2021;6:383.
90. Kil LP, de Bruijn MJ, van Nimwegen M, et al. Btk levels set the threshold for B-cell activation and negative selection of autoreactive B cells in mice. Blood 2012;119:3744-56.
91. Jin X, Xu Q, Pu C, et al. Therapeutic efficacy of anti-CD19 CAR-T cells in a mouse model of systemic lupus erythematosus. Cell Mol Immunol 2021;18:1896-903.
92. Lee OJ, Luk F, Korevaar SS, et al. The importance of dosing, timing, and (in)activation of adipose tissue-derived mesenchymal stromal cells on their immunomodulatory effects. Stem Cells Dev 2020;29:38-48.
93. Liu YJ, Miao HB, Lin S, Chen Z. Current progress in treating systemic lupus erythematosus using exosomes/MicroRNAs. Cell Transplant 2023;32:9636897221148775.
94. Fang T, Li B, Li M, et al. Engineered cell membrane vesicles expressing CD40 alleviate system lupus nephritis by intervening B cell activation. Small Methods 2023;7:e2200925.
95. Xu F, Fei Z, Dai H, et al. Mesenchymal stem cell-derived extracellular vesicles with high PD-L1 expression for autoimmune diseases treatment. Adv Mater 2022;34:2106265.
96. DeFronzo RA, Ferrannini E, Groop L, et al. Type 2 diabetes mellitus. Nat Rev Dis Primers 2015;1:15039.
97. Dong J, Wu B, Tian W. How to maximize the therapeutic effect of exosomes on skin wounds in diabetes mellitus: Review and discussion. Front Endocrinol 2023;14:1146991.
98. Zhang P, Lu J, Jing Y, Tang S, Zhu D, Bi Y. Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis†. Ann Med 2017;49:106-16.
99. Chen Q, Chen J, Liu Y, Qi S, Huang L. Exosome-based drug delivery systems for the treatment of diabetes and its complications: current opinion. Extracell Vesicles Circ Nucleic Acids 2023;4:502-17.
101. Gondaliya P, Sayyed AA, Bhat P, et al. Mesenchymal stem cell-derived exosomes loaded with miR-155 inhibitor ameliorate diabetic wound healing. Mol Pharm 2022;19:1294-308.
102. Born LJ, Chang KH, Shoureshi P, et al. HOTAIR-loaded mesenchymal stem/stromal cell extracellular vesicles enhance angiogenesis and wound healing. Adv Healthc Mater 2022;11:e2002070.
103. Chu Z, Huang Q, Ma K, et al. Novel neutrophil extracellular trap-related mechanisms in diabetic wounds inspire a promising treatment strategy with hypoxia-challenged small extracellular vesicles. Bioact Mater 2023;27:257-70.
104. Zhang D, Wu Y, Li Z, et al. MiR-144-5p, an exosomal miRNA from bone marrow-derived macrophage in type 2 diabetes, impairs bone fracture healing via targeting Smad1. J Nanobiotechnology 2021;19:226.
105. Wang N, Liu X, Tang Z, et al. Increased BMSC exosomal miR-140-3p alleviates bone degradation and promotes bone restoration by targeting Plxnb1 in diabetic rats. J Nanobiotechnology 2022;20:97.
106. Qiu P, Li M, Chen K, et al. Periosteal matrix-derived hydrogel promotes bone repair through an early immune regulation coupled with enhanced angio- and osteogenesis. Biomaterials 2020;227:119552.
107. Lin Z, Xiong Y, Meng W, et al. Exosomal PD-L1 induces osteogenic differentiation and promotes fracture healing by acting as an immunosuppressant. Bioact Mater 2022;13:300-11.
108. Roth GA, Johnson C, Abajobir A, et al. Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015. J Am Coll Cardiol 2017;70:1-25.
109. Vagnozzi RJ, Maillet M, Sargent MA, et al. An acute immune response underlies the benefit of cardiac stem cell therapy. Nature 2020;577:405-9.
110. Bolli R, Ghafghazi S. Stem cells: cell therapy for cardiac repair: what is needed to move forward? Nat Rev Cardiol 2017;14:257-8.
111. Sahoo S, Adamiak M, Mathiyalagan P, Kenneweg F, Kafert-Kasting S, Thum T. Therapeutic and diagnostic translation of extracellular vesicles in cardiovascular diseases: roadmap to the clinic. Circulation 2021;143:1426-49.
112. Du Y, Wu L, Wang L, Reiter RJ, Lip GYH, Ren J. Extracellular vesicles in cardiovascular diseases: From pathophysiology to diagnosis and therapy. Cytokine Growth Factor Rev 2023;74:40-55.
113. Ma J, Lei P, Chen H, et al. Advances in lncRNAs from stem cell-derived exosome for the treatment of cardiovascular diseases. Front Pharmacol 2022;13:986683.
114. Lai J, Huang C, Guo Y, Rao L. Engineered extracellular vesicles and their mimics in cardiovascular diseases. J Control Release 2022;347:27-43.
115. Chen Y, Zhao Y, Chen W, et al. MicroRNA-133 overexpression promotes the therapeutic efficacy of mesenchymal stem cells on acute myocardial infarction. Stem Cell Res Ther 2017;8:268.
116. Wei Z, Qiao S, Zhao J, et al. miRNA-181a over-expression in mesenchymal stem cell-derived exosomes influenced inflammatory response after myocardial ischemia-reperfusion injury. Life Sci 2019;232:116632.
117. Wei Z, Chen Z, Zhao Y, et al. Mononuclear phagocyte system blockade using extracellular vesicles modified with CD47 on membrane surface for myocardial infarction reperfusion injury treatment. Biomaterials 2021;275:121000.
118. Puhka M, Takatalo M, Nordberg ME, et al. Metabolomic Profiling of Extracellular Vesicles and Alternative Normalization Methods Reveal Enriched Metabolites and Strategies to Study Prostate Cancer-Related Changes. Theranostics 2017;7:3824-41.
119. Zhang M, Hu S, Liu L, et al. Engineered exosomes from different sources for cancer-targeted therapy. Signal Transduct Target Ther 2023;8:124.
120. Liu G, Wu J, Chen G, Shang A. The potential therapeutic value and application prospect of engineered exosomes in human diseases. Front Cell Dev Biol 2022;10:1051380.
121. Ovchinnikova LA, Terekhov SS, Ziganshin RH, et al. Reprogramming extracellular vesicles for protein therapeutics delivery. Pharmaceutics 2021;13:768.
122. A Study of exoASO-STAT6 (CDK-004) in patients with advanced hepatocellular carcinoma (HCC) and patients with liver metastases from either primary gastric cancer or colorectal cancer (CRC). Available from: https://clinicaltrials.gov/study/NCT05375604#study-overview [Last accessed on 24 Jan 2024].
123. A phase 1/2a study of CDK-003 in patients with cutaneous T-cell lymphoma (CTCL). (Part B). Available from: https://clinicaltrials.gov/study/NCT05156229?term=NCT05156229&rank=1 [Last accessed on 24 Jan 2024].
