REFERENCES
1. Vasseur D, Bigot L, Beshiri K, et al. Deciphering resistance mechanisms in cancer: final report of MATCH-R study with a focus on molecular drivers and PDX development. Mol Cancer. 2024;23:221.
2. Lei ZN, Tian Q, Teng QX, et al. Understanding and targeting resistance mechanisms in cancer. MedComm. 2023;4:e265.
3. Ramos A, Sadeghi S, Tabatabaeian H. Battling chemoresistance in cancer: root causes and strategies to uproot them. Int J Mol Sci. 2021;22:9451.
4. Wang X, He L, Huang X, et al. Recent progress of exosomes in multiple myeloma: pathogenesis, diagnosis, prognosis and therapeutic strategies. Cancers. 2021;13:1635.
5. Li Q, Ding Y, Shi Y, et al. 80 years of extracellular vesicles: from discovery to clinical translation. Extracell Vesicles Circ Nucl Acids. 2026;7:165-233.
6. Ratajczak MZ, Ratajczak J. Extracellular microvesicles/exosomes: discovery, disbelief, acceptance, and the future? Leukemia. 2020;34:3126-35.
7. Chen Y, Zhao Y, Yin Y, Jia X, Mao L. Mechanism of cargo sorting into small extracellular vesicles. Bioengineered. 2021;12:8186-201.
8. Wei H, Chen Q, Lin L, et al. Regulation of exosome production and cargo sorting. Int J Biol Sci. 2021;17:163-77.
9. Xie S, Zhang Q, Jiang L. Current knowledge on exosome biogenesis, cargo-sorting mechanism and therapeutic implications. Membranes. 2022;12:498.
10. Kotelevets L, Chastre E. Extracellular vesicles in colorectal cancer: from tumor growth and metastasis to biomarkers and nanomedications. Cancers. 2023;15:1107.
11. Fontana F, Carollo E, Melling GE, Carter DRF. Extracellular vesicles: emerging modulators of cancer drug resistance. Cancers. 2021;13:749.
12. Pan W, Miao Q, Yin W, et al. The role and clinical applications of exosomes in cancer drug resistance. Cancer Drug Resist. 2024;7:43.
13. Mashouri L, Yousefi H, Aref AR, Ahadi AM, Molaei F, Alahari SK. Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance. Mol Cancer. 2019;18:75.
14. Leonard GD, Fojo T, Bates SE. The role of ABC transporters in clinical practice. Oncologist. 2003;8:411-24.
15. Moitra K. Overcoming multidrug resistance in cancer stem cells. Biomed Res Int. 2015;2015:635745.
16. Januchowski R, Sterzyńska K, Zaorska K, et al. Analysis of MDR genes expression and cross-resistance in eight drug resistant ovarian cancer cell lines. J Ovarian Res. 2016;9:65.
17. Wang X, Qiao D, Chen L, et al. Chemotherapeutic drugs stimulate the release and recycling of extracellular vesicles to assist cancer cells in developing an urgent chemoresistance. Mol Cancer. 2019;18:182.
18. Wang X, Wang H, Jiang H, Qiao L, Guo C. Circular RNAcirc_0076305 promotes cisplatin (DDP) resistance of non-small cell lung cancer cells by regulating ABCC1 through miR-186-5p. Cancer Biother Radiopharm. 2023;38:293-304.
19. Corcoran C, Rani S, O’Brien K, et al. Docetaxel-resistance in prostate cancer: evaluating associated phenotypic changes and potential for resistance transfer via exosomes. PLoS One. 2012;7:e50999.
20. Misawa T, Toyoshima M, Kitatani K, et al. Involvement of small extracellular vesicle-derived TIE-1 in the chemoresistance of ovarian cancer cells. Cancer Treat Res Commun. 2021;27:100364.
21. Asare-Werehene M, Nakka K, Reunov A, et al. The exosome-mediated autocrine and paracrine actions of plasma gelsolin in ovarian cancer chemoresistance. Oncogene. 2020;39:1600-16.
22. Wang D, Zhao C, Xu F, et al. Cisplatin-resistant NSCLC cells induced by hypoxia transmit resistance to sensitive cells through exosomal PKM2. Theranostics. 2021;11:2860-75.
23. Au Yeung CL, Co NN, Tsuruga T, et al. Exosomal transfer of stroma-derived miR21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1. Nat Commun. 2016;7:11150.
24. Bai X, Ni J, Beretov J, Graham P, Li Y. Cancer stem cell in breast cancer therapeutic resistance. Cancer Treat Rev. 2018;69:152-63.
25. Hu JL, Wang W, Lan XL, et al. CAFs secreted exosomes promote metastasis and chemotherapy resistance by enhancing cell stemness and epithelial-mesenchymal transition in colorectal cancer. Mol Cancer. 2019;18:91.
26. Santos JC, Lima NDS, Sarian LO, Matheu A, Ribeiro ML, Derchain SFM. Exosome-mediated breast cancer chemoresistance via miR-155 transfer. Sci Rep. 2018;8:829.
27. Shan G, Zhou X, Gu J, et al. Downregulated exosomal microRNA-148b-3p in cancer associated fibroblasts enhance chemosensitivity of bladder cancer cells by downregulating the Wnt/β-catenin pathway and upregulating PTEN. Cell Oncol. 2021;44:45-59.
28. Zhan Y, Zhou Z, Zhu Z, et al. Exosome-transmitted LUCAT1 promotes stemness transformation and chemoresistance in bladder cancer by binding to IGF2BP2. J Exp Clin Cancer Res. 2025;44:80.
29. Shen M, Dong C, Ruan X, et al. Chemotherapy-induced extracellular vesicle miRNAs promote breast cancer stemness by targeting ONECUT2. Cancer Res. 2019;79:3608-21.
30. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252-64.
31. Ichim TE, Zhong Z, Kaushal S, et al. Exosomes as a tumor immune escape mechanism: possible therapeutic implications. J Transl Med. 2008;6:37.
32. Théry C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol. 2009;9:581-93.
33. Liu C, Yu S, Zinn K, et al. Murine mammary carcinoma exosomes promote tumor growth by suppression of NK cell function. J Immunol. 2006;176:1375-85.
34. Chen R, Xu X, Qian Z, et al. The biological functions and clinical applications of exosomes in lung cancer. Cell Mol Life Sci. 2019;76:4613-33.
35. Clayton A, Mitchell JP, Court J, Linnane S, Mason MD, Tabi Z. Human tumor-derived exosomes down-modulate NKG2D expression. J Immunol. 2008;180:7249-58.
36. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324:1029-33.
37. Lehuédé C, Dupuy F, Rabinovitch R, Jones RG, Siegel PM. Metabolic plasticity as a determinant of tumor growth and metastasis. Cancer Res. 2016;76:5201-8.
38. Su G, Qian J, Wang Y, et al. Platelet-derived exosomal LINC00183 facilitate colorectal cancer malignant progression driven by histone lactylation through stabilizing ENO1. Cell Death Dis. 2025;16:593.
39. Yu L, Liebenberg K, Shen Y, et al. Tumor-derived arachidonic acid reprograms neutrophils to promote immune suppression and therapy resistance in triple-negative breast cancer. Immunity. 2025;58:909-25.e7.
40. Yang J, Zhang M, Zhang X, et al. Glioblastoma-derived exosomes promote lipid accumulation and induce ferroptosis in dendritic cells via the NRF2/GPX4 pathway. Front Immunol. 2024;15:1439191.
41. Vakili-Ghartavol Z, Deli H, Shadboorestan A, Sahebnasagh R, Motevaseli E, Ghahremani MH. Exosomes and their distinct integrins transfer the characteristics of oxaliplatin- and 5-FU-resistant behaviors in colorectal cancer cells. Mol Med. 2025;31:49.
42. Wang W, Chen J, Wang S, et al. MFGE8 induces anti-PD-1 therapy resistance by promoting extracellular vesicle sorting of PD-L1. Cell Rep Med. 2025;6:101922.
43. Zhuang L, Zhang B, Liu X, et al. Exosomal miR-21-5p derived from cisplatin-resistant SKOV3 ovarian cancer cells promotes glycolysis and inhibits chemosensitivity of its progenitor SKOV3 cells by targeting PDHA1. Cell Biol Int. 2021;45:2140-9.
44. Liu Z, Zhao W, Yang R. MiR-1246 is responsible for lung cancer cells-derived exosomes-mediated promoting effects on lung cancer stemness via targeting TRIM17. Environ Toxicol. 2022;37:2651-9.
45. Yu Q, Zhang Y, Tian Y, et al. Exosomal circ_FMN2 derived from the serum of colorectal cancer patients promotes cancer progression by miR-338-3p/MSI1 axis. Appl Biochem Biotechnol. 2023;195:7322-37.
46. Hirpara J, Thuya WL, Cheow SH, et al. Tumor-derived extracellular vesicles convey solute transporters to induce bioenergetic dependence shift contributing to treatment resistance. Theranostics. 2024;14:6350-69.
47. Serratì S, Guida M, Di Fonte R, et al. Circulating extracellular vesicles expressing PD1 and PD-L1 predict response and mediate resistance to checkpoint inhibitors immunotherapy in metastatic melanoma. Mol Cancer. 2022;21:20.
48. Yang H, Xie S, Liang B, et al. Exosomal IDH1 increases the resistance of colorectal cancer cells to 5-Fluorouracil. J Cancer. 2021;12:4862-72.
49. Wang Z, Li Y, Mao R, et al. DNAJB8 in small extracellular vesicles promotes Oxaliplatin resistance through TP53/MDR1 pathway in colon cancer. Cell Death Dis. 2022;13:151.
50. Chabon JJ, Hamilton EG, Kurtz DM, et al. Integrating genomic features for non-invasive early lung cancer detection. Nature. 2020;580:245-51.
51. Clancy JW, D’Souza-Schorey C. Tumor-derived extracellular vesicles: multifunctional entities in the tumor microenvironment. Annu Rev Pathol. 2023;18:205-29.
52. Lai X, Zhong J, Zhang B, Zhu T, Liao R. Exosomal non-coding RNAs: novel regulators of macrophage-linked intercellular communication in lung cancer and inflammatory lung diseases. Biomolecules. 2023;13:536.
53. Casagrande GMS, Silva MO, Reis RM, Leal LF. Liquid biopsy for lung cancer: up-to-date and perspectives for screening programs. Int J Mol Sci. 2023;24:2505.
54. Gupta DK. Editorial: exosomal biomarkers: roles in diagnostics and therapeutics. Front Mol Biosci. 2022;9:1127540.
55. Ura A, Saito T, Motoi T, et al. A case of primary distal-type epithelioid sarcoma of the lumbar vertebra with a review of literature. Virchows Arch. 2021;479:393-400.
56. Wang H, Hou L, Li A, Duan Y, Gao H, Song X. Expression of serum exosomal microRNA-21 in human hepatocellular carcinoma. Biomed Res Int. 2014;2014:864894.
57. Tian XP, Wang CY, Jin XH, et al. Acidic microenvironment up-regulates exosomal miR-21 and miR-10b in early-stage hepatocellular carcinoma to promote cancer cell proliferation and metastasis. Theranostics. 2019;9:1965-79.
58. Fortunato O, Boeri M, Moro M, et al. Mir-660 is downregulated in lung cancer patients and its replacement inhibits lung tumorigenesis by targeting MDM2-p53 interaction. Cell Death Dis. 2014;5:e1564.
59. He L, He X, Lim LP, et al. A microRNA component of the p53 tumour suppressor network. Nature. 2007;447:1130-4.
60. He L, Lin M, Shen J, Qi H. Emerging role of exosomal long non-coding RNAs in lung cancer. Mol Biol Rep. 2022;49:4989-97.
61. Pan R, Zhou H. Exosomal transfer of lncRNA H19 promotes erlotinib resistance in non-small cell lung cancer via miR-615-3p/ATG7 axis. Cancer Manag Res. 2020;12:4283-97.
62. Zhang R, Xia Y, Wang Z, et al. Serum long non coding RNA MALAT-1 protected by exosomes is up-regulated and promotes cell proliferation and migration in non-small cell lung cancer. Biochem Biophys Res Commun. 2017;490:406-14.
63. Guo X, Gao C, Yang DH, Li S. Exosomal circular RNAs: a chief culprit in cancer chemotherapy resistance. Drug Resist Updat. 2023;67:100937.
64. Zhu H, Yang W, Cheng Q, Yang S. Circ_0010235 regulates HOXA10 expression to promote malignant phenotypes and radioresistance in non-small cell lung cancer cells via decoying miR-588. Balkan Med J. 2022;39:255-66.
65. Zhao J, Yan W, Huang W, Li Y. Circ_0010235 facilitates lung cancer development and immune escape by regulating miR-636/PDL1 axis. Thorac Cancer. 2022;13:965-76.
66. Zhu L, Zhao L, Wang Q, et al. Circulating exosomal miRNAs and cancer early diagnosis. Clin Transl Oncol. 2022;24:393-406.
67. Ludwig S, Floros T, Theodoraki MN, et al. Suppression of lymphocyte functions by plasma exosomes correlates with disease activity in patients with head and neck cancer. Clin Cancer Res. 2017;23:4843-54.
68. Chen G, Huang AC, Zhang W, et al. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature. 2018;560:382-6.
69. Ricklefs FL, Alayo Q, Krenzlin H, et al. Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles. Sci Adv. 2018;4:eaar2766.
70. Zhou Y, Miao J, Wu H, et al. PD-1 and PD-L1 expression in 132 recurrent nasopharyngeal carcinoma: the correlation with anemia and outcomes. Oncotarget. 2017;8:51210-23.
71. Fan Y, Che X, Qu J, et al. Exosomal PD-L1 retains immunosuppressive activity and is associated with gastric cancer prognosis. Ann Surg Oncol. 2019;26:3745-55.
72. Cordonnier M, Nardin C, Chanteloup G, et al. Tracking the evolution of circulating exosomal-PD-L1 to monitor melanoma patients. J Extracell Vesicles. 2020;9:1710899.
73. Tan C, Sun W, Xu Z, et al. Small extracellular vesicles deliver TGF-β1 and promote adriamycin resistance in breast cancer cells. Mol Oncol. 2021;15:1528-42.
74. Pote MS, Gacche RN. ATP-binding cassette efflux transporters and MDR in cancer. Drug Discov Today. 2023;28:103537.
75. Sajid A, Rahman H, Ambudkar SV. Advances in the structure, mechanism and targeting of chemoresistance-linked ABC transporters. Nat Rev Cancer. 2023;23:762-79.
76. Robey RW, Pluchino KM, Hall MD, Fojo AT, Bates SE, Gottesman MM. Revisiting the role of ABC transporters in multidrug-resistant cancer. Nat Rev Cancer. 2018;18:452-64.
77. Bharathiraja P, Yadav P, Sajid A, Ambudkar SV, Prasad NR. Natural medicinal compounds target signal transduction pathways to overcome ABC drug efflux transporter-mediated multidrug resistance in cancer. Drug Resist Updat. 2023;71:101004.
78. Zattoni IF, Delabio LC, Dutra JP, et al. Targeting breast cancer resistance protein (BCRP/ABCG2): functional inhibitors and expression modulators. Eur J Med Chem. 2022;237:114346.
79. Palmulli R, Jackson HK, Edgar JR. Tethered exosomes containing the matrix metalloproteinase MT1-MMP contribute to extracellular matrix degradation. J Extracell Vesicles. 2025;14:e70122.
80. Oh S, Lee SS, Jin H, et al. A disintegrin and metallopeptidase domain (ADAM) 12, ADAM 17 mRNA and ADAM10 protein hold potential as biomarkers for detection of early gastric cancer. Sci Rep. 2025;15:763.
81. Mitchell MI, Ma J, Carter CL, Loudig O. Circulating exosome cargoes contain functionally diverse cancer biomarkers: from biogenesis and function to purification and potential translational utility. Cancers. 2022;14:3350.
82. Choi DY, You S, Jung JH, et al. Extracellular vesicles shed from gefitinib-resistant nonsmall cell lung cancer regulate the tumor microenvironment. Proteomics. 2014;14:1845-56.
83. Forte D, Pellegrino RM, Falvo P, et al. Parallel single-cell metabolic analysis and extracellular vesicle profiling reveal vulnerabilities with prognostic significance in acute myeloid leukemia. Nat Commun. 2024;15:10878.
84. Tan S, Tang H, Wang Y, et al. Tumor cell-derived exosomes regulate macrophage polarization: Emerging directions in the study of tumor genesis and development. Heliyon. 2023;9:e19296.
85. Zhou Q, Wei S, Wang H, et al. T cell-derived exosomes in tumor immune modulation and immunotherapy. Front Immunol. 2023;14:1130033.
86. Vulpis E, Soriani A, Cerboni C, Santoni A, Zingoni A. Cancer exosomes as conveyors of stress-induced molecules: new players in the modulation of NK cell response. Int J Mol Sci. 2019;20:611.
87. Wang X, Luo G, Zhang K, et al. Hypoxic tumor-derived exosomal miR-301a mediates M2 macrophage polarization via PTEN/PI3Kγ to promote pancreatic cancer metastasis. Cancer Res. 2018;78:4586-98.
88. Song J, Yang P, Li X, et al. Esophageal cancer-derived extracellular vesicle miR-21-5p contributes to EMT of ESCC cells by disorganizing macrophage polarization. Cancers. 2021;13:4122.
89. Yang C, Dou R, Wei C, et al. Tumor-derived exosomal microRNA-106b-5p activates EMT-cancer cell and M2-subtype TAM interaction to facilitate CRC metastasis. Mol Ther. 2021;29:2088-107.
90. Pang X, Wang SS, Zhang M, et al. OSCC cell-secreted exosomal CMTM6 induced M2-like macrophages polarization via ERK1/2 signaling pathway. Cancer Immunol Immunother. 2021;70:1015-29.
91. Cheng Z, Wang L, Wu C, Huang L, Ruan Y, Xue W. Tumor-derived exosomes induced M2 macrophage polarization and promoted the metastasis of osteosarcoma cells through Tim-3. Arch Med Res. 2021;52:200-10.
92. Moradi-Chaleshtori M, Bandehpour M, Soudi S, Mohammadi-Yeganeh S, Hashemi SM. In vitro and in vivo evaluation of anti-tumoral effect of M1 phenotype induction in macrophages by miR-130 and miR-33 containing exosomes. Cancer Immunol Immunother. 2021;70:1323-39.
93. Moradi-Chaleshtori M, Shojaei S, Mohammadi-Yeganeh S, Hashemi SM. Transfer of miRNA in tumor-derived exosomes suppresses breast tumor cell invasion and migration by inducing M1 polarization in macrophages. Life Sci. 2021;282:119800.
94. Smyth LA, Ratnasothy K, Tsang JY, et al. CD73 expression on extracellular vesicles derived from CD4+ CD25+ Foxp3+ T cells contributes to their regulatory function. Eur J Immunol. 2013;43:2430-40.
95. Clayton A, Al-Taei S, Webber J, Mason MD, Tabi Z. Cancer exosomes express CD39 and CD73, which suppress T cells through adenosine production. J Immunol. 2011;187:676-83.
96. Yang Y, Bucan V, Baehre H, von der Ohe J, Otte A, Hass R. Acquisition of new tumor cell properties by MSC-derived exosomes. Int J Oncol. 2015;47:244-52.
97. Zhou WJ, Zhang J, Xie F, et al. CD45RO-CD8+ T cell-derived exosomes restrict estrogen-driven endometrial cancer development via the ERβ/miR-765/PLP2/Notch axis. Theranostics. 2021;11:5330-45.
98. Labani-Motlagh A, Israelsson P, Ottander U, et al. Differential expression of ligands for NKG2D and DNAM-1 receptors by epithelial ovarian cancer-derived exosomes and its influence on NK cell cytotoxicity. Tumour Biol. 2016;37:5455-66.
99. Lundholm M, Schröder M, Nagaeva O, et al. Prostate tumor-derived exosomes down-regulate NKG2D expression on natural killer cells and CD8+ T cells: mechanism of immune evasion. PLoS One. 2014;9:e108925.
100. Xie Y, Bai O, Zhang H, et al. Membrane-bound HSP70-engineered myeloma cell-derived exosomes stimulate more efficient CD8+ CTL- and NK-mediated antitumour immunity than exosomes released from heat-shocked tumour cells expressing cytoplasmic HSP70. J Cell Mol Med. 2010;14:2655-66.
101. Salvi V, Gianello V, Busatto S, et al. Exosome-delivered microRNAs promote IFN-α secretion by human plasmacytoid DCs via TLR7. JCI Insight. 2018;3:98204.
102. Crescitelli R, Lässer C, Lötvall J. Isolation and characterization of extracellular vesicle subpopulations from tissues. Nat Protoc. 2021;16:1548-80.
103. Khan NA, Asim M, Biswas KH, et al. Exosome nanovesicles as potential biomarkers and immune checkpoint signaling modulators in lung cancer microenvironment: recent advances and emerging concepts. J Exp Clin Cancer Res. 2023;42:221.
104. Yu D, Li Y, Wang M, et al. Exosomes as a new frontier of cancer liquid biopsy. Mol Cancer. 2022;21:56.
105. Dong X, Lin Y, Li K, et al. Consensus statement on extracellular vesicles in liquid biopsy for advancing laboratory medicine. Clin Chem Lab Med. 2025;63:465-82.
106. Wang J, Chang S, Li G, Sun Y. Application of liquid biopsy in precision medicine: opportunities and challenges. Front Med. 2017;11:522-7.
107. Wu M, Ouyang Y, Wang Z, et al. Isolation of exosomes from whole blood by integrating acoustics and microfluidics. Proc Natl Acad Sci U S A. 2017;114:10584-9.
108. Lin S, Yu Z, Chen D, et al. Progress in microfluidics-based exosome separation and detection technologies for diagnostic applications. Small. 2020;16:e1903916.
109. Tang H, Yu D, Zhang J, et al. The new advance of exosome-based liquid biopsy for cancer diagnosis. J Nanobiotechnology. 2024;22:610.
110. Lee H, Lee J, Lee SG, Doyle PS. Hydrogel-based colorimetric assay for multiplexed microRNA detection in a microfluidic device. Anal Chem. 2020;92:5750-5.
111. Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020;367:eaau6977.
112. Théry C, Witwer KW, Aikawa E, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles. 2018;7:1535750.
113. Heitzer E, Haque IS, Roberts CES, Speicher MR. Current and future perspectives of liquid biopsies in genomics-driven oncology. Nat Rev Genet. 2019;20:71-88.
114. Zheng Y, Hasan A, Nejadi Babadaei MM, et al. Exosomes: multiple-targeted multifunctional biological nanoparticles in the diagnosis, drug delivery, and imaging of cancer cells. Biomed Pharmacother. 2020;129:110442.
115. Kurniawati I, Liu MC, Hsieh CL, Do AD, Sung SY. Targeting castration-resistant prostate cancer using mesenchymal stem cell exosomes for therapeutic microRNA-let-7c delivery. Front Biosci. 2022;27:256.
116. Guo Z, Gao S, Wang Z, et al. Engineered RGD-treg-exos targeted delivery of miR-218-5p to activate mitophagy and attenuate podocyte injury in diabetic kidney disease. Adv Sci. 2025;12:e12034.
117. 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.
118. Zhang H, Xing J, Sun M, et al. Engineered exosomes for targeted microRNA delivery to reverse liver fibrosis. Biomaterials. 2026;324:123510.
119. Ma C, Liu K, Wang F, et al. Neutrophil membrane-engineered Panax ginseng root-derived exosomes loaded miRNA 182-5p targets NOX4/Drp-1/NLRP3 signal pathway to alleviate acute lung injury in sepsis: experimental studies. Int J Surg. 2024;110:72-86.
120. Lamichhane TN, Jeyaram A, Patel DB, et al. Oncogene knockdown via active loading of small RNAs into extracellular vesicles by sonication. Cell Mol Bioeng. 2016;9:315-24.
121. Tian J, Han Z, Song D, et al. Engineered exosome for drug delivery: recent development and clinical applications. Int J Nanomedicine. 2023;18:7923-40.
122. Cheng Y, Zeng Q, Han Q, Xia W. Effect of pH, temperature and freezing-thawing on quantity changes and cellular uptake of exosomes. Protein Cell. 2019;10:295-9.
123. Hosseini NF, Amini R, Ramezani M, Saidijam M, Hashemi SM, Najafi R. AS1411 aptamer-functionalized exosomes in the targeted delivery of doxorubicin in fighting colorectal cancer. Biomed Pharmacother. 2022;155:113690.
124. Qu M, Lin Q, Huang L, et al. Dopamine-loaded blood exosomes targeted to brain for better treatment of Parkinson’s disease. J Control Release. 2018;287:156-66.
125. Salarpour S, Forootanfar H, Pournamdari M, Ahmadi-Zeidabadi M, Esmaeeli M, Pardakhty A. Paclitaxel incorporated exosomes derived from glioblastoma cells: comparative study of two loading techniques. Daru. 2019;27:533-9.
126. Kim MS, Haney MJ, Zhao Y, et al. Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomedicine. 2016;12:655-64.
127. 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.
128. Liang G, Zhu Y, Ali DJ, et al. Engineered exosomes for targeted co-delivery of miR-21 inhibitor and chemotherapeutics to reverse drug resistance in colon cancer. J Nanobiotechnology. 2020;18:10.
129. Abas BI, Demirbolat GM, Cevik O. Wharton jelly-derived mesenchymal stem cell exosomes induce apoptosis and suppress EMT signaling in cervical cancer cells as an effective drug carrier system of paclitaxel. PLoS One. 2022;17:e0274607.
130. Qiu L, Wang J, Chen M, Chen F, Tu W. Exosomal microRNA‑146a derived from mesenchymal stem cells increases the sensitivity of ovarian cancer cells to docetaxel and taxane via a LAMC2‑mediated PI3K/Akt axis. Int J Mol Med. 2020;46:609-20.
131. Zhang X, Liu L, Tang M, Li H, Guo X, Yang X. The effects of umbilical cord-derived macrophage exosomes loaded with cisplatin on the growth and drug resistance of ovarian cancer cells. Drug Dev Ind Pharm. 2020;46:1150-62.
132. Luo H, Zhou Y, Zhang J, et al. NK cell-derived exosomes enhance the anti-tumor effects against ovarian cancer by delivering cisplatin and reactivating NK cell functions. Front Immunol. 2022;13:1087689.
133. Aqil F, Munagala R, Jeyabalan J, Agrawal AK, Gupta R. Exosomes for the enhanced tissue bioavailability and efficacy of curcumin. AAPS J. 2017;19:1691-702.
134. Aqil F, Jeyabalan J, Agrawal AK, et al. Exosomal delivery of berry anthocyanidins for the management of ovarian cancer. Food Funct. 2017;8:4100-7.
135. Huang W, Qu M, Li L, Liu T, Lin M, Yu X. SiRNA in MSC-derived exosomes silences CTGF gene for locomotor recovery in spinal cord injury rats. Stem Cell Res Ther. 2021;12:334.
136. Geng Y, Long X, Zhang Y, et al. FTO-targeted siRNA delivery by MSC-derived exosomes synergistically alleviates dopaminergic neuronal death in Parkinson's disease via m6A-dependent regulation of ATM mRNA. J Transl Med. 2023;21:652.
137. Jeong K, Yu YJ, You JY, Rhee WJ, Kim JA. Exosome-mediated microRNA-497 delivery for anti-cancer therapy in a microfluidic 3D lung cancer model. Lab Chip. 2020;20:548-57.
138. Lou G, Song X, Yang F, et al. Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma. J Hematol Oncol. 2015;8:122.
139. Lou G, Chen L, Xia C, et al. MiR-199a-modified exosomes from adipose tissue-derived mesenchymal stem cells improve hepatocellular carcinoma chemosensitivity through mTOR pathway. J Exp Clin Cancer Res. 2020;39:4.
140. Wong ST, Zhang XQ, Zhuang JT, Chan HL, Li CH, Leung GK. MicroRNA-21 inhibition enhances in vitro chemosensitivity of temozolomide-resistant glioblastoma cells. Anticancer Res. 2012;32:2835-41.
141. Wang JJ, Wang ZY, Chen R, et al. Macrophage-secreted exosomes delivering miRNA-21 inhibitor can regulate BGC-823 cell proliferation. Asian Pac J Cancer Prev. 2015;16:4203-9.
142. Usman WM, Pham TC, Kwok YY, et al. Efficient RNA drug delivery using red blood cell extracellular vesicles. Nat Commun. 2018;9:2359.
143. Lin Y, Wu J, Gu W, et al. Exosome-liposome hybrid nanoparticles deliver CRISPR/Cas9 system in MSCs. Adv Sci. 2018;5:1700611.
144. Belhadj Z, He B, Deng H, et al. A combined “eat me/don’t eat me” strategy based on extracellular vesicles for anticancer nanomedicine. J Extracell Vesicles. 2020;9:1806444.
145. Lv Q, Cheng L, Lu Y, et al. Thermosensitive exosome-liposome hybrid nanoparticle-mediated chemoimmunotherapy for improved treatment of metastatic peritoneal cancer. Adv Sc. 2020;7:2000515.
146. Cheng L, Zhang X, Tang J, Lv Q, Liu J. Gene-engineered exosomes-thermosensitive liposomes hybrid nanovesicles by the blockade of CD47 signal for combined photothermal therapy and cancer immunotherapy. Biomaterials. 2021;275:120964.
147. Clayton A, Harris CL, Court J, Mason MD, Morgan BP. Antigen-presenting cell exosomes are protected from complement-mediated lysis by expression of CD55 and CD59. Eur J Immunol. 2003;33:522-31.
148. Li L, He D, Guo Q, et al. Exosome-liposome hybrid nanoparticle codelivery of TP and miR497 conspicuously overcomes chemoresistant ovarian cancer. J Nanobiotechnology. 2022;20:50.
149. Hu Y, Li X, Zhang Q, et al. Exosome-guided bone targeted delivery of Antagomir-188 as an anabolic therapy for bone loss. Bioact Mater. 2021;6:2905-13.
150. Xitong D, Xiaorong Z. Targeted therapeutic delivery using engineered exosomes and its applications in cardiovascular diseases. Gene. 2016;575:377-84.
151. Liu C, Zhang W, Li Y, et al. Microfluidic sonication to assemble exosome membrane-coated nanoparticles for immune evasion-mediated targeting. Nano Lett. 2019;19:7836-44.
152. Khongkow M, Yata T, Boonrungsiman S, Ruktanonchai UR, Graham D, Namdee K. Surface modification of gold nanoparticles with neuron-targeted exosome for enhanced blood-brain barrier penetration. Sci Rep. 2019;9:8278.
153. Srivastava A, Amreddy N, Babu A, et al. Nanosomes carrying doxorubicin exhibit potent anticancer activity against human lung cancer cells. Sci Rep. 2016;6:38541.
154. Wang J, Chen P, Dong Y, et al. Designer exosomes enabling tumor targeted efficient chemo/gene/photothermal therapy. Biomaterials. 2021;276:121056.
155. Wang X, Xu Z, Wang J, et al. A mitochondria-targeted biomimetic nanomedicine capable of reversing drug resistance in colorectal cancer through mitochondrial dysfunction. Adv Sci. 2025;12:e2410630.
156. Pan S, Zhang Y, Huang M, et al. Urinary exosomes-based engineered nanovectors for homologously targeted chemo-chemodynamic prostate cancer therapy via abrogating EGFR/AKT/NF-kB/IkB signaling. Biomaterials. 2021;275:120946.
157. Piffoux M, Silva AKA, Wilhelm C, Gazeau F, Tareste D. Modification of extracellular vesicles by fusion with liposomes for the design of personalized biogenic drug delivery systems. ACS Nano. 2018;12:6830-42.
158. Geng Y, Xia W, Zheng X, et al. Targeted delivery of FAK siRNA by engineered exosomes to reverse cetuximab resistance via activating paraptosis in colon cancer. Apoptosis. 2024;29:1959-77.
159. Gao K, Xi W, Ni J, et al. Genetically modified extracellular vesicles loaded with activated gasdermin D potentially inhibit prostate-specific membrane antigen-positive prostate carcinoma growth and enhance immunotherapy. Biomaterials. 2025;315:122894.
160. Wang G, Xie L, Li B, et al. A nanounit strategy reverses immune suppression of exosomal PD-L1 and is associated with enhanced ferroptosis. Nat Commun. 2021;12:5733.
161. Fan Y, Zhou Y, Lu M, Si H, Li L, Tang B. Responsive dual-targeting exosome as a drug carrier for combination cancer immunotherapy. Research. 2021;2021:9862876.
162. Wei X, Sun L, Deng J, Yang Q, Zhao J, Zhou S. A multifunctional exosome with dual homeostasis disruption augments cGAS-STING-mediated tumor immunotherapy by boosting ferroptosis. Nano Lett. 2024;24:14263-72.
163. Bhatta R, Han J, Liu Y, et al. Metabolic tagging of extracellular vesicles and development of enhanced extracellular vesicle based cancer vaccines. Nat Commun. 2023;14:8047.
164. Huang L, Rong Y, Tang X, et al. Engineered exosomes as an in situ DC-primed vaccine to boost antitumor immunity in breast cancer. Mol Cancer. 2022;21:45.
165. Li J, Li J, Peng Y, Du Y, Yang Z, Qi X. Dendritic cell derived exosomes loaded neoantigens for personalized cancer immunotherapies. J Control Release. 2023;353:423-33.
166. Zhu L, Kalimuthu S, Gangadaran P, et al. Exosomes derived from natural killer cells exert therapeutic effect in melanoma. Theranostics. 2017;7:2732-45.
167. Cochran AM, Kornbluth J. Extracellular vesicles from the human natural killer cell line NK3.3 have broad and potent anti-tumor activity. Front Cell Dev Biol. 2021;9:698639.
168. Zhou W, Zhou Y, Chen X, et al. Pancreatic cancer-targeting exosomes for enhancing immunotherapy and reprogramming tumor microenvironment. Biomaterials. 2021;268:120546.
169. 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.
170. Sun H, Zhang AH, Liu SB, et al. Cell metabolomics identify regulatory pathways and targets of magnoline against prostate cancer. J Chromatogr B Analyt Technol Biomed Life Sci. 2018;1102-3:143-51.
171. Aqil F, Kausar H, Agrawal AK, et al. Exosomal formulation enhances therapeutic response of celastrol against lung cancer. Exp Mol Pathol. 2016;101:12-21.
172. Wang H, Feng J, Ao F, et al. Tumor-derived exosomal microRNA-7-5p enhanced by verbascoside inhibits biological behaviors of glioblastoma in vitro and in vivo. Mol Ther Oncolytics. 2021;20:569-82.
173. Zhang J, Zhang HD, Yao YF, Zhong SL, Zhao JH, Tang JH. β-elemene reverses chemoresistance of breast cancer cells by reducing resistance transmission via exosomes. Cell Physiol Biochem. 2015;36:2274-86.
174. Jang JY, Lee JK, Jeon YK, Kim CW. Exosome derived from epigallocatechin gallate treated breast cancer cells suppresses tumor growth by inhibiting tumor-associated macrophage infiltration and M2 polarization. BMC Cancer. 2013;13:421.
175. Taverna S, Fontana S, Monteleone F, et al. Curcumin modulates chronic myelogenous leukemia exosomes composition and affects angiogenic phenotype via exosomal miR-21. Oncotarget. 2016;7:30420-39.
176. Cui J, Wang X, Li J, et al. Immune exosomes loading self-assembled nanomicelles traverse the blood-brain barrier for chemo-immunotherapy against glioblastoma. ACS Nano. 2023;17:1464-84.
177. Dehghani L, Khojasteh A, Soleimani M, et al. Safety of intraparenchymal injection of allogenic placenta mesenchymal stem cells derived exosome in patients undergoing decompressive craniectomy following malignant middle cerebral artery infarct, a pilot randomized clinical trial. Int J Prev Med. 2022;13:7.
178. Pak H, Hadizadeh A, Heirani-Tabasi A, et al. Safety and efficacy of injection of human placenta mesenchymal stem cells derived exosomes for treatment of complex perianal fistula in non-Crohn’s cases: clinical trial phase I. J Gastroenterol Hepatol. 2023;38:539-47.
179. Ha DH, Kim SD, Lee J, et al. Toxicological evaluation of exosomes derived from human adipose tissue-derived mesenchymal stem/stromal cells. Regul Toxicol Pharmacol. 2020;115:104686.
180. Zhou P, Li D, Chen GH, Wang Y. [Serum-free culture of umbilical cord mesenchymal stem cells]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2013;21:1256-60. Available from: https://www.semanticscholar.org/paper/%5BSerum-free-culture-of-umbilical-cord-mesenchymal-Zhou-Li/66a957c437a556f7b178ffec41d5ed46458fa8c3. [Last accessed on 7 May 2026].
181. Witwer KW, Van Balkom BWM, Bruno S, et al. Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications. J Extracell Vesicles. 2019;8:1609206.
182. Aung T, Chapuy B, Vogel D, et al. Exosomal evasion of humoral immunotherapy in aggressive B-cell lymphoma modulated by ATP-binding cassette transporter A3. Proc Natl Acad Sci U S A. 2011;108:15336-41.
183. Barok M, Puhka M, Yazdi N, Joensuu H. Extracellular vesicles as modifiers of antibody-drug conjugate efficacy. J Extracell Vesicles. 2021;10:e12070.
184. Kamerkar S, Leng C, Burenkova O, et al. Exosome-mediated genetic reprogramming of tumor-associated macrophages by exoASO-STAT6 leads to potent monotherapy antitumor activity. Sci Adv. 2022;8:eabj7002.
185. Binenbaum Y, Fridman E, Yaari Z, et al. Transfer of miRNA in macrophage-derived exosomes induces drug resistance in pancreatic adenocarcinoma. Cancer Res. 2018;78:5287-99.
186. Munoz JL, Bliss SA, Greco SJ, Ramkissoon SH, Ligon KL, Rameshwar P. Delivery of functional anti-miR-9 by mesenchymal stem cell-derived exosomes to glioblastoma multiforme cells conferred chemosensitivity. Mol Ther Nucleic Acids. 2013;2:e126.
187. 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.
188. Hui B, Lu C, Wang J, et al. Engineered exosomes for co-delivery of PGM5-AS1 and oxaliplatin to reverse drug resistance in colon cancer. J Cell Physiol. 2022;237:911-33.
189. Wang R, Liang Q, Zhang X, Di Z, Wang X, Di L. Tumor-derived exosomes reversing TMZ resistance by synergistic drug delivery for glioma-targeting treatment. Colloids Surf B Biointerfaces. 2022;215:112505.
190. Zhao C, Qiu L, Wu D, et al. Targeted reversal of multidrug resistance in ovarian cancer cells using exosome‑encapsulated tetramethylpyrazine. Mol Med Rep. 2024;29:25.
191. Jiang L, Zhang Y, Guo L, Liu C, Wang P, Ren W. Exosomal microRNA-107 reverses chemotherapeutic drug resistance of gastric cancer cells through HMGA2/mTOR/P-gp pathway. BMC Cancer. 2021;21:1290.
192. Vader P, Mol EA, Pasterkamp G, Schiffelers RM. Extracellular vesicles for drug delivery. Adv Drug Deliv Rev. 2016;106:148-56.
193. Wiklander OPB, Brennan MÁ, Lötvall J, Breakefield XO, El Andaloussi S. Advances in therapeutic applications of extracellular vesicles. Sci Transl Med. 2019;11:eaav8521.
194. Lener T, Gimona M, Aigner L, et al. Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper. J Extracell Vesicles. 2015;4:30087.
195. Yáñez-Mó M, Siljander PR, Andreu Z, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4:27066.
196. 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.
197. Li Z, Yang L, Wang H, Binzel DW, Williams TM, Guo P. Non-small-cell lung cancer regression by siRNA delivered through exosomes that display EGFR RNA aptamer. Nucleic Acid Ther. 2021;31:364-74.
198. Zhang C, Wu Q, Gong Y, et al. Biomimetic exosomal vesicles loaded with siRNA improves antitumor immune responses by inhibiting the secretion of tumor-derived exosome PD-L1. Int Immunopharmacol. 2024;129:111659.
199. Lu Z, Zuo B, Jing R, et al. Dendritic cell-derived exosomes elicit tumor regression in autochthonous hepatocellular carcinoma mouse models. J Hepatol. 2017;67:739-48.
200. Zhong X, Zhou Y, Cao Y, et al. Enhanced antitumor efficacy through microwave ablation combined with a dendritic cell-derived exosome vaccine in hepatocellular carcinoma. Int J Hyperthermia. 2020;37:1210-8.
201. Morishima Y, Kawabori M, Yamazaki K, et al. Intravenous administration of mesenchymal stem cell-derived exosome alleviates spinal cord injury by regulating neutrophil extracellular trap formation through exosomal miR-125a-3p. Int J Mol Sci. 2024;25:2406.
202. Zhao Q, Mo Z, Zeng L, Yuan Y, Wang Y, Wang Y. Construction and evaluation of hepatic targeted drug delivery system with hydroxycamptothecin in stem cell-derived exosomes. Molecules. 2024;29:5174.
203. Sanchez-Diaz M, Quiñones-Vico MI, Sanabria de la Torre R, et al. Biodistribution of mesenchymal stromal cells after administration in animal models and humans: a systematic review. J Clin Med. 2021;10:2925.
204. Betzer O, Perets N, Angel A, et al. In vivo neuroimaging of exosomes using gold nanoparticles. ACS Nano. 2017;11:10883-93.
205. Popowski KD, López de Juan Abad B, George A, et al. Inhalable exosomes outperform liposomes as mRNA and protein drug carriers to the lung. Extracell Vesicle. 2022;1:100002.
206. Cao JY, Wang B, Tang TT, et al. Exosomal miR-125b-5p deriving from mesenchymal stem cells promotes tubular repair by suppression of p53 in ischemic acute kidney injury. Theranostics. 2021;11:5248-66.
207. Li X, Chen C, Wang Z, et al. Elevated exosome-derived miRNAs predict osimertinib resistance in non-small cell lung cancer. Cancer Cell Int. 2021;21:428.
208. Yang B, Teng F, Chang L, et al. Tumor-derived exosomal circRNA_102481 contributes to EGFR-TKIs resistance via the miR-30a-5p/ROR1 axis in non-small cell lung cancer. Aging. 2021;13:13264-86.
209. Tang S, Zheng K, Tang Y, Li Z, Zou T, Liu D. Overexpression of serum exosomal HOTAIR is correlated with poor survival and poor response to chemotherapy in breast cancer patients. J Biosci. 2019;44:37.
210. Wang H, Liu L, Liu Q, et al. Identification of upregulated exosomal miRNAs between A2780 and A2780/DDP human ovarian cancer cells by high-throughput sequencing. J Ovarian Res. 2023;16:94.
211. Wang Y, Niu X, Cheng Y, et al. Exosomal PD-L1 predicts response with immunotherapy in NSCLC patients. Clin Exp Immunol. 2022;208:316-22.
212. Del Re M, Marconcini R, Pasquini G, et al. PD-L1 mRNA expression in plasma-derived exosomes is associated with response to anti-PD-1 antibodies in melanoma and NSCLC. Br J Cancer. 2018;118:820-4.
213. de Miguel-Perez D, Russo A, Arrieta O, et al. Extracellular vesicle PD-L1 dynamics predict durable response to immune-checkpoint inhibitors and survival in patients with non-small cell lung cancer. J Exp Clin Cancer Res. 2022;41:186.
214. Zhang C, Fan Y, Che X, et al. Anti-PD-1 therapy response predicted by the combination of exosomal PD-L1 and CD28. Front Oncol. 2020;10:760.
215. Lei Z, Chen X, Chen K, et al. Exosome-like vesicles encapsulated with specific microRNAs accelerate burn wound healing and ameliorate scarring. J Nanobiotechnology. 2025;23:264.
216. Li S, Zhang M, Zhang H, et al. Exosomal long noncoding RNA lnc-GNAQ-6:1 may serve as a diagnostic marker for gastric cancer. Clin Chim Acta. 2020;501:252-7.
217. Yang L, Yang Z, Liu Z, Qi N, Tao L. Diagnostic value of plasma-derived exosomal miR-223 for epithelial ovarian cancer. BMC Womens Health. 2024;24:150.
218. Escudier B, Dorval T, Chaput N, et al. Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial. J Transl Med. 2005;3:10.
219. Morse MA, Garst J, Osada T, et al. A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer. J Transl Med. 2005;3:9.
220. 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.
221. Lotfy A, AboQuella NM, Wang H. Mesenchymal stromal/stem cell (MSC)-derived exosomes in clinical trials. Stem Cell Res Ther. 2023;14:66.
222. Tieu A, Lalu MM, Slobodian M, et al. An analysis of mesenchymal stem cell-derived extracellular vesicles for preclinical use. ACS Nano. 2020;14:9728-43.
223. Kok VC, Yu CC. Cancer-derived exosomes: their role in cancer biology and biomarker development. Int J Nanomedicine. 2020;15:8019-36.
224. Staubach S, Bauer FN, Tertel T, et al. Scaled preparation of extracellular vesicles from conditioned media. Adv Drug Deliv Rev. 2021;177:113940.
225. Freitas D, Balmaña M, Poças J, et al. Different isolation approaches lead to diverse glycosylated extracellular vesicle populations. J Extracell Vesicles. 2019;8:1621131.
226. Vulto AG, Jaquez OA. The process defines the product: what really matters in biosimilar design and production? Rheumatology. 2017;56:iv14-29.
227. Rohde E, Pachler K, Gimona M. Manufacturing and characterization of extracellular vesicles from umbilical cord-derived mesenchymal stromal cells for clinical testing. Cytotherapy. 2019;21:581-92.
228. Paganini C, Capasso Palmiero U, Pocsfalvi G, Touzet N, Bongiovanni A, Arosio P. Scalable production and isolation of extracellular vesicles: available sources and lessons from current industrial bioprocesses. Biotechnol J. 2019;14:e1800528.
229. Lőrincz ÁM, Timár CI, Marosvári KA, et al. Effect of storage on physical and functional properties of extracellular vesicles derived from neutrophilic granulocytes. J Extracell Vesicles. 2014;3:25465.
230. Charoenviriyakul C, Takahashi Y, Nishikawa M, Takakura Y. Preservation of exosomes at room temperature using lyophilization. Int J Pharm. 2018;553:1-7.
