Diagnostic and therapeutic applications of melanoma-derived exosomes in nanomedicine

Li Li , Xin Zheng , Jingru Shi , Fu Zhao , Yisheng Chen , Hongling Jia , Jianan Chen , Xiaojing Wang , Peng Luo , Lin Zhang , Zhiwen Luo , Qi Sun , Li Lin , Zhijie Zhao

Microstructures ›› 2026, Vol. 6 ›› Issue (4) : 20260102

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Microstructures ›› 2026, Vol. 6 ›› Issue (4) :20260102 DOI: 10.20517/microstructures.2026.03
Review
Diagnostic and therapeutic applications of melanoma-derived exosomes in nanomedicine
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Abstract

Melanoma remains challenging due to pronounced heterogeneity, early metastasis, and dynamic treatment resistance. Conventional tissue biopsy and imaging provide essential information but are limited by invasiveness, sampling bias, and an inability to capture longitudinal tumor-immune evolution. As endogenous bio-nanomaterials, small extracellular vesicles/exosomes circulate stably in body fluids and carry multi-omic cargo (DNA, RNA, proteins, lipids), enabling minimally invasive liquid biopsy and real-time disease monitoring. Beyond diagnostics, engineered exosomal nanomaterials can be functionalized and loaded with therapeutic payloads to improve targeted delivery and support combination regimens, including immunotherapy. This review highlights mechanistic roles of exosomes in melanoma progression, summarizes key liquid-biopsy biomarkers (e.g., exosomal PD-L1 and EV-miRNA/protein signatures), and discusses translational barriers such as standardization, scalable manufacturing, safety, and clinical validation.

Keywords

Melanoma / exosomal nanomaterials / small extracellular vesicles / liquid biopsy / immunotherapy monitoring / exosomal PD-L1 / engineered exosomes / targeted delivery / theranostics

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Li Li, Xin Zheng, Jingru Shi, Fu Zhao, Yisheng Chen, Hongling Jia, Jianan Chen, Xiaojing Wang, Peng Luo, Lin Zhang, Zhiwen Luo, Qi Sun, Li Lin, Zhijie Zhao. Diagnostic and therapeutic applications of melanoma-derived exosomes in nanomedicine. Microstructures, 2026, 6 (4) : 20260102 DOI:10.20517/microstructures.2026.03

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References

[1]

Keilholz U,Dummer R.ESMO consensus conference recommendations on the management of metastatic melanoma: under the auspices of the ESMO Guidelines Committee.Ann Oncol2020;31:1435-48

[2]

Atkins MB,Fisher DE.The state of melanoma: emergent challenges and opportunities.Clin Cancer Res2021;27:2678-97 PMCID:PMC8127340

[3]

Li H,Xiahou Z,Zhao F.The cellular signaling crosstalk between memory B cells and tumor cells in nasopharyngeal carcinoma cannot be overlooked: Their involvement in tumor progression and treatment strategy is significant.J Cancer2025;16:288-314 PMCID:PMC11660138

[4]

Huang SK.Liquid biopsy utility for the surveillance of cutaneous malignant melanoma patients.Mol Oncol2015;10:450-63 PMCID:PMC5307330

[5]

Sivapalan L,Canzoniero JV.Liquid biopsy approaches to capture tumor evolution and clinical outcomes during cancer immunotherapy.J Immunother Cancer2023;11:e005924 PMCID:PMC9853269

[6]

Patel RP,Smith LK,Mcarthur GA.The therapeutic potential of targeting minimal residual disease in melanoma.Clin Transl Med2023;13:e1197 PMCID:PMC10040726

[7]

Tirosh I,Prakadan SM.Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq.Science2016;352:189-96

[8]

Whiteside TL.Biology of extracellular vesicles and the potential of tumor-derived vesicles for subverting immunotherapy of cancer.J Immunother Cancer2025;13:e010376 PMCID:PMC11759217

[9]

Zou Y,Li G,Hu S.Clinical applications of extracellular vesicles: recent advances and emerging trends.Front Bioeng Biotechnol2025;13:1671963 PMCID:PMC12598036

[10]

Welsh JA,O'driscoll L.Minimal information for studies of extracellular vesicles (MISEV2023): from basic to advanced approaches.J Extracell Vesicle2024;13:e12404

[11]

Ragni E.Extracellular vesicles: recent advances and perspectives.Front Biosci2025;30:36405

[12]

Tang H,Zhang J.The new advance of exosome-based liquid biopsy for cancer diagnosis.J Nanobiotechnol2024;22:610 PMCID:PMC11463159

[13]

Ghanam J,Chetty VK.Unravelling the significance of extracellular vesicle-associated DNA in cancer biology and its potential clinical applications.J Extracell Vesicle2025;14:e70047 PMCID:PMC11911540

[14]

Andre M,Miles JS,Ruiz MA.Diagnostic potential of exosomal extracellular vesicles in oncology.BMC Cancer2024;24:322 PMCID:PMC10921614

[15]

Li Z,Cao Y.Extracellular RNA in melanoma: advances, challenges, and opportunities.Front Cell Dev Biol2023;11:1141543 PMCID:PMC10192583

[16]

Zhan Y,Zeng H,Chen X.Extracellular vesicle-derived non-coding RNAs in remodeling melanoma.Biomed Pharmacother2024;172:116213

[17]

Slusher N,Nonaka T.Liquid biopsy for diagnostic and prognostic evaluation of melanoma.Front Cell Dev Biol2024;12:1420360 PMCID:PMC11327088

[18]

Liu JJJ,To SKY.Exosomes in cancer nanomedicine: biotechnological advancements and innovations.Mol Cancer2025;24:166 PMCID:PMC12144782

[19]

Ovchinnikova LA.Extracellular vesicles as a source of biomarkers for cancer diagnosis.Acta Nat2025;17:28-40 PMCID:PMC12322890

[20]

Babaei S,Abbasi-Kenarsari H,Kazemi T.Exosome-based immunotherapy as an innovative therapeutic approach in melanoma.Cell Commun Signal2024;22:527 PMCID:PMC11526674

[21]

Di Bella MA.Overview and update on extracellular vesicles: considerations on exosomes and their application in modern medicine.Biology2022;11:804 PMCID:PMC9220244

[22]

Zhang Y,Chen Y.Minimal information for studies of extracellular vesicles (MISEV): ten-year evolution (2014-2023).Pharmaceutics2024;16:1394 PMCID:PMC11597804

[23]

Di Bella MA.Extracellular vesicles: diagnostic and therapeutic applications in cancer.Biology2024;13:716 PMCID:PMC11446462

[24]

Yang C,Duan Y,Wan M.Extracellular vesicles and their engineering strategies, delivery systems, and biomedical applications.J Controlled Release2024;365:1089-123

[25]

Zhang Q,Higginbotham JN,Coffey RJ.Comprehensive isolation of extracellular vesicles and nanoparticles.Nat Protoc2023;18:1462-87 PMCID:PMC10445291

[26]

Carney RP,Bozkurt BT.Harnessing extracellular vesicle heterogeneity for diagnostic and therapeutic applications.Nat Nanotechnol2024;20:14-25 PMCID:PMC11781840

[27]

Li B,Xu W,Ji C.Advances of extracellular vesicles isolation and detection frontier technology: from heterogeneity analysis to clinical application.J Nanobiotechnol2025;23:678 PMCID:PMC12519844

[28]

Woo H,Park HG.Bridging laboratory innovation to translational research and commercialization of extracellular vesicle isolation and detection.Biosens Bioelectron2025;282:117475 PMCID:PMC12076185

[29]

Poggio M,Pai C.Suppression of exosomal PD-L1 induces systemic anti-tumor immunity and memory.Cell2019;177:414-27.e13 PMCID:PMC6499401

[30]

Urzì O,Crescitelli R.Extracellular vesicles in uveal melanoma - Biological roles and diagnostic value.Cancer Lett2025;615:217531

[31]

Dong X,Li K.Consensus statement on extracellular vesicles in liquid biopsy for advancing laboratory medicine.Clin Chem Lab Med2025;63:465-82

[32]

Asleh K,Taylor C,Djeungoue-Petga M.Extracellular vesicle-based liquid biopsy biomarkers and their application in precision immuno-oncology.Biomark Res2023;11:99 PMCID:PMC10655470

[33]

Liu J,Xin W.Exosomal non-coding RNAs: a new approach to melanoma diagnosis and therapeutic strategy.Curr Med Chem2024;31:6084-109

[34]

Ricciardi E,Ziccheddu G.Metastatic melanoma: liquid biopsy as a new precision medicine approach.Int J Mol Sci2023;24:4014 PMCID:PMC9962821

[35]

Minami S,Ochiya T.Extracellular vesicle-based liquid biopsies in cancer: Future biomarkers for oral cancer.Transl Oncol2023;38:101786 PMCID:PMC10509717

[36]

Mondal SK.Proteomic profiles of melanoma cell-derived exosomes in plasma: discovery of potential biomarkers of melanoma progression.Melanoma Res2021;31:472-5 PMCID:PMC8429197

[37]

Lattmann E,Tognetti M.Size-exclusion chromatography combined with DIA-MS enables deep proteome profiling of extracellular vesicles from melanoma plasma and serum.Cell Mol Life Sci2024;81:90 PMCID:PMC10867102

[38]

Clancy JW.Tumor-derived extracellular vesicles: multifunctional entities in the tumor microenvironment.Annu Rev Pathol Mech Dis2023;18:205-29 PMCID:PMC10410237

[39]

Helvind NM,Chakera AH.Stage-specific risk of recurrence and death from melanoma in Denmark, 2008-2021: a national observational cohort study of 25 720 patients with stage IA to IV melanoma.JAMA Dermatol2023;159:1213 PMCID:PMC10472263

[40]

Spiliopoulou P,Spreafico A.Promising and minimally invasive biomarkers: targeting melanoma.Cells2023;13:19 PMCID:PMC10777980

[41]

Serratì S,Di Fonte R.Circulating extracellular vesicles expressing PD1 and PD-L1 predict response and mediate resistance to checkpoint inhibitors immunotherapy in metastatic melanoma.Mol Cancer2022;21:20 PMCID:PMC8764806

[42]

Sun L,Zhao Q.Dynamic change of PD-L2 on circulating plasma extracellular vesicles as a predictor of treatment response in melanoma patients receiving anti-PD-1 therapy.J Extracell Vesicle2025;14:e70054

[43]

Hsu C,Mohammed JS.Exosomes as key mediators in immune and cancer cell interactions: insights in melanoma progression and therapy.Arch Dermatol Res2025;317:729

[44]

Serrano DR,Anaya BJ.Exosome-based drug delivery: a next-generation platform for cancer, infection, neurological and immunological diseases, gene therapy and regenerative medicine.Pharmaceutics2025;17:1336 PMCID:PMC12567338

[45]

Johnson V,Kumar US.Surface-engineered extracellular vesicles in cancer immunotherapy.Cancers2023;15:2838 PMCID:PMC10216164

[46]

Kim HI,Zhu Y,Han Y.Recent advances in extracellular vesicles for therapeutic cargo delivery.Exp Mol Med2024;56:836-49 PMCID:PMC11059217

[47]

Chen Y,Ho Y.Exosomes: a review of biologic function, diagnostic and targeted therapy applications, and clinical trials.J Biomed Sci2024;31:67 PMCID:PMC11238361

[48]

Brezgin S,Yudaeva A.Basic guide for approaching drug delivery with extracellular vesicles.Int J Mol Sci2024;25:10401 PMCID:PMC11476574

[49]

Abbasi-malati Z,Milani SZ.Tumorigenic and tumoricidal properties of exosomes in cancers; a forward look.Cell Commun Signal2024;22:130 PMCID:PMC10870553

[50]

Xia Y,Liu G.Immunogenicity of extracellular vesicles.Adv Mater2024;36:2403199

[51]

Ziogas DC,Koutouratsas T,Gogas H.Mechanisms of resistance to immune checkpoint inhibitors in melanoma: what we have to overcome?.Cancer Treat Rev2023;113:102499

[52]

Fernandez MF,Sosman J.New approaches to targeted therapy in Melanoma.Cancers2023;15:3224 PMCID:PMC10296143

[53]

Yin G,Huang Z.Efficacy of radiotherapy combined with immune checkpoint inhibitors in patients with melanoma: a systemic review and meta-analysis.Melanoma Res2022;32:71-8

[54]

Van Delen M,Wouters K,Cools N.A systematic review and meta-analysis of clinical trials assessing safety and efficacy of human extracellular vesicle-based therapy.J Extracell Vesicle2024;13:e12458 PMCID:PMC11220457

[55]

Xu G,Fu Z.Extracellular vesicle-based drug overview: research landscape, quality control and nonclinical evaluation strategies.Sig Transduct Target Ther2025;10:255 PMCID:PMC12350758

[56]

Su X,Li Q.Extracellular vesicles: a review of their therapeutic potentials, sources, biodistribution, and administration routes.Int J Nanomed2025;20:3175-99 PMCID:PMC11913029

[57]

Kang M,Blenkiron C.Biodistribution of extracellular vesicles following administration into animals: a systematic review.J Extracell Vesicle2021;10:e12085 PMCID:PMC8224174

[58]

Chen T,Su W,Liu X.Extracellular vesicles as vital players in drug delivery: a focus on clinical disease treatment.Front Bioeng Biotechnol2025;13:1600227 PMCID:PMC12116468

[59]

Humbert C,Drut I.GMP-compliant process for the manufacturing of an extracellular vesicles-enriched secretome product derived from cardiovascular progenitor cells suitable for a phase I clinical trial.J Extracell Vesicle2025;14:e70145 PMCID:PMC12365392

[60]

Akbani R,Aksoy BA.Genomic classification of cutaneous melanoma.Cell2015;161:1681-96

[61]

Moran B,Perry AS.Epigenetics of malignant melanoma.Semin Cancer Biol2018;51:80-8

[62]

Sarkar D,Baguley BC,Askarian-Amiri ME.Epigenetic regulation in human melanoma: past and future.Epigenetics2015;10:103-21 PMCID:PMC4622872

[63]

Mannavola F,Cives M.Extracellular vesicles and epigenetic modifications are hallmarks of melanoma progression.Int J Mol Sci2019;21:52 PMCID:PMC6981648

[64]

Kalluri R.The biology,function, and biomedical applications of exosomes.Science2020;367:eaau6977 PMCID:PMC7717626

[65]

Willms E,Mäger I,Vader P.Extracellular vesicle heterogeneity: subpopulations, isolation techniques, and diverse functions in cancer progression.Front Immunol2018;9:738 PMCID:PMC5936763

[66]

Zaborowski MP,Breakefield XO.Extracellular vesicles: composition, biological relevance, and methods of study.Bioscience2015;65:783-97 PMCID:PMC4776721

[67]

Yáñez-mó M,Andreu Z.Biological properties of extracellular vesicles and their physiological functions.J Extracell Vesicle2015;4:27066

[68]

Lespagnol A,Beekman C.Exosome secretion, including the DNA damage-induced p53-dependent secretory pathway, is severely compromised in TSAP6/Steap3-null mice.Cell Death Differ2008;15:1723-33

[69]

Payandeh Z,Somi MH.PD-1/PD-L1-dependent immune response in colorectal cancer.J Cell Physiol2020;235:5461-75

[70]

Jiang Y,Fu J.Progress and challenges in precise treatment of tumors with PD-1/PD-L1 blockade.Front Immunol2020;11:339 PMCID:PMC7080697

[71]

Wang B,Ma H.Regulatory effect of PD1/PD-Ligand 1 (PD-L1) on treg cells in patients with idiopathic pulmonary fibrosis.Med Sci Monit2020;26:927577 PMCID:PMC7786833

[72]

Shergold AL,Nibbs RJ.Understanding and overcoming the resistance of cancer to PD-1/PD-L1 blockade.Pharmacol Res2019;145:104258

[73]

Cloughesy TF,Orpilla JR.Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.Nat Med2019;25:477-86

[74]

Chen G,Zhang W.Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response.Nature2018;560:382-6

[75]

Ricklefs FL,Krenzlin H.Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles.Sci Adv2018;4:eaar2766 PMCID:PMC5842038

[76]

Theodoraki M,Hoffmann TK,Whiteside TL.Clinical significance of PD-L1+ exosomes in plasma of head and neck cancer patients.Clin Cancer Res2018;24:896-905 PMCID:PMC6126905

[77]

Yang Y,Chan L.Exosomal PD-L1 harbors active defense function to suppress T cell killing of breast cancer cells and promote tumor growth.Cell Res2018;28:862-4 PMCID:PMC6082826

[78]

Fleming V,Weller C.Melanoma extracellular vesicles generate immunosuppressive myeloid cells by upregulating PD-L1 via TLR4 signaling.Cancer Res2019;79:4715-28

[79]

Du Z,Zhang H,Wang J.Melanoma-derived small extracellular vesicles remodel the systemic onco-immunity via disrupting hematopoietic stem cell proliferation and differentiation.Cancer Lett2022;545:215841

[80]

Maus RLG,Nevala WK.Human melanoma-derived extracellular vesicles regulate dendritic cell maturation.Front Immunol2017;8:358 PMCID:PMC5372822

[81]

Valenti R,Filipazzi P.Human tumor-released microvesicles promote the differentiation of myeloid cells with transforming growth factor-β-mediated suppressive activity on t lymphocytes.Cancer Res2006;66:9290-8

[82]

Hosseini R,Yousefi H.The roles of tumor-derived exosomes in altered differentiation, maturation and function of dendritic cells.Mol Cancer2021;20:83 PMCID:PMC8170799

[83]

Marton A,Kusz E.Melanoma cell-derived exosomes alter macrophage and dendritic cell functions in vitro.Immunol Lett2012;148:34-8

[84]

Düchler M,Peczek L,Sztiller-Sikorska M.Melanoma-derived extracellular vesicles bear the potential for the induction of antigen-specific tolerance.Cells2019;8:665 PMCID:PMC6679195

[85]

Sharma P,Ferrone S,Whiteside TL.Melanoma cell-derived exosomes in plasma of melanoma patients suppress functions of immune effector cells.Sci Rep2020;10:92 PMCID:PMC6952363

[86]

Whiteside TL.Immunosuppressive functions of melanoma cell-derived exosomes in plasma of melanoma patients.Front Cell Dev Biol2023;10:1080925 PMCID:PMC9853022

[87]

Crucitta S,Marconcini R.TGF-β mRNA levels in circulating extracellular vesicles are associated with response to anti-PD1 treatment in metastatic melanoma.Front Mol Biosci2024;11:1288677 PMCID:PMC11021649

[88]

Tatischeff I.Extracellular vesicle-DNA: the next liquid biopsy biomarker for early cancer diagnosis?.Cancers2023;15:1456 PMCID:PMC10000627

[89]

Belviso I,Mileo A.The role of fibroblasts in melanoma development: from tumor microenvironment remodeling to pre-metastatic niche formation.Int J Mol Sci2025;26:6132 PMCID:PMC12249749

[90]

Lu M.Exosomal PD-L1 in cancer and other fields: recent advances and perspectives.Front Immunol2024;15:1395332 PMCID:PMC11079227

[91]

Chen J,Miao F.PDL1-positive exosomes suppress antitumor immunity by inducing tumor-specific CD8+ T cell exhaustion during metastasis.Cancer Sci2021;112:3437-54 PMCID:PMC8409314

[92]

Liu N,Yin M.Inhibition of xCT suppresses the efficacy of anti-PD-1/L1 melanoma treatment through exosomal PD-L1-induced macrophage M2 polarization.Mol Ther2021;29:2321-34 PMCID:PMC8261162

[93]

Christofides A,Yeo A,Charest A.The complex role of tumor-infiltrating macrophages.Nat Immunol2022;23:1148-56 PMCID:PMC10754321

[94]

Gerloff D,Moritz RK.Melanoma-derived exosomal miR-125b-5p educates tumor associated macrophages (TAMs) by targeting lysosomal acid lipase A (LIPA).Cancers2020;12:464 PMCID:PMC7072270

[95]

Wang R,Hou B.An iPSC-derived exosome-pulsed dendritic cell vaccine boosts antitumor immunity in melanoma.Mol Ther2023;31:2376-90 PMCID:PMC10422017

[96]

Tucci M,Passarelli A,Cives M.Exosomes in melanoma: a role in tumor progression, metastasis and impaired immune system activity.Oncotarget2018;9:20826-37 PMCID:PMC5945529

[97]

Zhou J,Wang W.Melanoma-released exosomes directly activate the mitochondrial apoptotic pathway of CD4+ T cells through their microRNA cargo.Exp Cell Res2018;371:364-71

[98]

Li X,Yang L,Qian Q.TIM-3 shuttled by MV3 cells-secreted exosomes inhibits CD4+ T cell immune function and induces macrophage M2 polarization to promote the growth and metastasis of melanoma cells.Transl Oncol2022;18:101334 PMCID:PMC8808081

[99]

De Cicco P,Ianaro A.The new era of cancer immunotherapy: targeting myeloid-derived suppressor cells to overcome immune evasion.Front Immunol2020;11:1680 PMCID:PMC7406792

[100]

Peinado H,Lavotshkin S.Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET.Nat Med2012;18:883-91

[101]

Peinado H,Matei IR.Pre-metastatic niches: organ-specific homes for metastases.Nat Rev Cancer2017;17:302-17

[102]

Kim J,Sengupta R.Replication study: melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET.eLife2018;7:e39944

[103]

Rinderknecht M.Tumor lymphangiogenesis and melanoma metastasis.J Cell Physiol2008;216:347-54

[104]

Hood JL,Wickline SA.Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis.Cancer Res2011;71:3792-801

[105]

García-Silva S,Nogués L.Melanoma-derived small extracellular vesicles induce lymphangiogenesis and metastasis through an NGFR-dependent mechanism.Nat Cancer2021;2:1387-405 PMCID:PMC8697753

[106]

Hu T.Melanoma-derived exosomes induce reprogramming fibroblasts into cancer-associated fibroblasts via Gm26809 delivery.Cell Cycle2019;18:3085-94 PMCID:PMC6816427

[107]

Shelton M,Nsengimana J,Newton-Bishop J.The role of CAF derived exosomal microRNAs in the tumour microenvironment of melanoma.Biochim Biophys Acta2021;1875:188456

[108]

Benito-Martín A,García-Silva S.Extracellular vesicles and melanoma: new perspectives on tumor microenvironment and metastasis.Front Cell Dev Biol2023;10:1061982 PMCID:PMC9871288

[109]

Wang C,Chang X.Melanoma-derived exosomes endow fibroblasts with an invasive potential via miR-21 target signaling pathway.Cancer Manag Res2020;12:12965-74

[110]

Tagliatela AC,Hibshman PS.Coronin 1C inhibits melanoma metastasis through regulation of MT1-MMP-containing extracellular vesicle secretion.Sci Rep2020;10:11958 PMCID:PMC7371684

[111]

Pavlides S,Castello-Cros R.The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma.Cell Cycle2014;8:3984-4001

[112]

Lazar I,Dauvillier S.Adipocyte exosomes promote melanoma aggressiveness through fatty acid oxidation: a novel mechanism linking obesity and cancer.Cancer Res2016;76:4051-7

[113]

Clement E,Attané C.Adipocyte extracellular vesicles carry enzymes and fatty acids that stimulate mitochondrial metabolism and remodeling in tumor cells.EMBO J2020;39:EMBJ2019102525 PMCID:PMC6996584

[114]

Medhin LB,Warburton L,Gray ES.Extracellular vesicles as a liquid biopsy for melanoma: are we there yet?.Semin Cancer Biol2023;89:92-8

[115]

Wu N,Sun Q.Circulating microRNAs as diagnostic biomarkers for melanoma: a systematic review and meta-analysis.BMC Cancer2023;23:414 PMCID:PMC10165832

[116]

Hu C,Lv M.Potentiality of exosomal proteins as novel cancer biomarkers for liquid biopsy.Front Immunol2022;13:792046 PMCID:PMC9218252

[117]

Wang M,Peng Y,Hui W.Exosomal LGALS9 in the cerebrospinal fluid of glioblastoma patients suppressed dendritic cell antigen presentation and cytotoxic T-cell immunity.Cell Death Dis2020;11:896 PMCID:PMC7582167

[118]

Shimada Y,Kudo Y.Serum-derived exosomal PD-L1 expression to predict anti-PD-1 response and in patients with non-small cell lung cancer.Sci Rep2021;11:7830 PMCID:PMC8035184

[119]

Kluszczynska K.Extracellular vesicles-based cell-cell communication in melanoma: new perspectives in diagnostics and therapy.Int J Mol Sci2023;24:965 PMCID:PMC9865538

[120]

Van Niel G,Raposo G.Shedding light on the cell biology of extracellular vesicles.Nat Rev Mol Cell Biol2018;19:213-28

[121]

Théry C,Aikawa E.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 Vesicle2018;7:1535750 PMCID:PMC6322352

[122]

Ullah M.The future of bioorthogonal-chemistry for targeting of exosomes in precision medicine.Oncotarget2022;13:1303-4 PMCID:PMC9725980

[123]

Rayamajhi S,Tetlow AL,Bansal A.Extracellular vesicles as liquid biopsy biomarkers across the cancer journey: from early detection to recurrence.Clin Chem2024;70:206-19 PMCID:PMC12374260

[124]

Xia C,To KKW.CD39/CD73/A2AR pathway and cancer immunotherapy.Mol Cancer2023;22:44 PMCID:PMC9979453

[125]

Kurago Z,Shi H.Inhibitors of the CD73-adenosinergic checkpoint as promising combinatory agents for conventional and advanced cancer immunotherapy.Front Immunol2023;14:1212209 PMCID:PMC10330720

[126]

Saigí M,Barbie DA.Unraveling the intricacies of CD73/adenosine signaling: the pulmonary immune and stromal microenvironment in lung cancer.Cancers2023;15:5706 PMCID:PMC10705793

[127]

Turiello R,Morretta E.Exosomal CD73 from serum of patients with melanoma suppresses lymphocyte functions and is associated with therapy resistance to anti-PD-1 agents.J Immunother Cancer2022;10:e004043 PMCID:PMC8915288

[128]

Yang Y,Xu Y.The progress and prospects of targeting the adenosine pathway in cancer immunotherapy.Biomark Res2025;13:75 PMCID:PMC12090549

[129]

Rodrigues-junior DM,Lim SK,Moustakas A.Extracellular vesicles and transforming growth factor β signaling in cancer.Front Cell Dev Biol2022;10:849938 PMCID:PMC9043557

[130]

De Miguel-Perez D,Gunasekaran M.Baseline extracellular vesicle TGF-β is a predictive biomarker for response to immune checkpoint inhibitors and survival in non-small cell lung cancer.Cancer2022;129:521-30

[131]

Biagioni A,Menicacci B.uPAR-expressing melanoma exosomes promote angiogenesis by VE-Cadherin, EGFR and uPAR overexpression and rise of ERK1,2 signaling in endothelial cells.Cell Mol Life Sci2020;78:3057-72 PMCID:PMC8004497

[132]

Porcelli L,De Summa S.uPAR+ extracellular vesicles: a robust biomarker of resistance to checkpoint inhibitor immunotherapy in metastatic melanoma patients.J Immunother Cancer2021;9:e002372 PMCID:PMC8112420

[133]

Serratì S,Porcelli L.Circulating extracellular vesicles are monitoring biomarkers of anti-PD1 response and enhancer of tumor progression and immunosuppression in metastatic melanoma.J Exp Clin Cancer Res2023;42:251 PMCID:PMC10538246

[134]

Cordonnier M,Chanteloup G.Tracking the evolution of circulating exosomal-PD-L1 to monitor melanoma patients.J Extracell Vesicle2020;9:1710899 PMCID:PMC6968537

[135]

Hur JY.Characteristics and clinical application of extracellular vesicle-derived DNA.Cancers2021;13:3827 PMCID:PMC8345206

[136]

Waldenmaier M,Schönfelder J.Comparative panel sequencing of DNA variants in cf-, ev- and tumorDNA for pancreatic ductal adenocarcinoma patients.Cancers2022;14:1074 PMCID:PMC8870073

[137]

Miceli RT,Nose Y.Extracellular vesicles, RNA sequencing, and bioinformatic analyses: challenges, solutions, and recommendations.J Extracell Vesicle2024;13:e70005 PMCID:PMC11613500

[138]

Li M,Liu G.A promising frontier of circulating messenger RNA in liquid biopsy: from mechanisms to clinical applications.Int J Cancer2025;157:1519-37 PMCID:PMC12375855

[139]

Bamodu OA,Pisanic TR.Harnessing liquid biopsies: exosomes and ctDNA as minimally invasive biomarkers for precision cancer medicine.J Liquid Biopsy2023;2:100126 PMCID:PMC11863985

[140]

Sánchez-Herrero E,Robado De Lope L,Romero A.Circulating tumor DNA as a cancer biomarker: an overview of biological features and factors that may impact on ctDNA analysis.Front Oncol2022;12:943253 PMCID:PMC9350013

[141]

Tsering T,Wu T,Burnier JV.Extracellular vesicle-associated DNA: ten years since its discovery in human blood.Cell Death Dis2024;15:668 PMCID:PMC11393322

[142]

Shen Y,Liao L,Wang Y.Plasma exosome-derived connexin43 as a promising biomarker for melanoma patients.BMC Cancer2023;23:242 PMCID:PMC10012581

[143]

Lim SY,Diefenbach RJ.Circulating MicroRNAs: functional biomarkers for melanoma prognosis and treatment.Mol Cancer2025;24:99 PMCID:PMC11951542

[144]

De Martino E,Azzalini E.A group of three miRNAs can act as candidate circulating biomarkers in liquid biopsies from melanoma patients.Front Med2023;10:1180799 PMCID:PMC10301821

[145]

Trilla-Fuertes L,Laso-García F.Protein content of extracellular vesicles from patients with advanced melanoma changes upon progression to anti-PD1 therapy.Sci Rep2026;16:5891 PMCID:PMC12894721

[146]

Bollard S,Casalou C.Proteomic and metabolomic profiles of plasma-derived Extracellular Vesicles differentiate melanoma patients from healthy controls.Transl Oncol2024;50:102152 PMCID:PMC11736400

[147]

Sirivolu S,Neviani P,Berry JL.Comparative single vesicle analysis of aqueous humor extracellular vesicles before and after radiation in uveal melanoma eyes.Int J Mol Sci2024;25:6035 PMCID:PMC11172950

[148]

Luz Pessuti C,Ribeiro KS.Characterization of Extracellular vesicles isolated from different liquid biopsies of uveal melanoma patients.J Circ Biomark2022;11:36-47 PMCID:PMC9238429

[149]

Beasley AB,Isaacs TW.Future perspectives of uveal melanoma blood based biomarkers.Br J Cancer2022;126:1511-28 PMCID:PMC9130512

[150]

Marsavela G,Pereira MR.Detection of clinical progression through plasma ctDNA in metastatic melanoma patients: a comparison to radiological progression.Br J Cancer2021;126:401-8 PMCID:PMC8810871

[151]

De Simoni E,Gandini S.Circulating tumor DNA-based assessment of molecular residual disease in non-metastatic melanoma.Cancer Treat Rev2024;129:102788

[152]

Fathi M,Moghimi A.Combined cancer immunotherapy based on targeting adenosine pathway and PD-1/PDL-1 axis.Expert Opin Ther Targets2024;28:757-77

[153]

Shan Z.Targeting ferroptosis, pyroptosis and necroptosis for cancer immunotherapy in melanoma: mechanistic insights and clinical perspectives.Front Immunol2025;16:1629620 PMCID:PMC12605190

[154]

Sato YT,Sawada S.Engineering hybrid exosomes by membrane fusion with liposomes.Sci Rep2016;6:21933 PMCID:PMC4766490

[155]

Lee J,Na K.GMP manufacturing of umbilical cord blood mesenchymal stem cell-released exosomes and verification of wound healing efficacy.Nanotheranostics2025;9:95-109 PMCID:PMC11980038

[156]

Yang F,Guan X.Exosomes and mimics as novel delivery platform for cancer therapy.Front Pharmacol2022;13:1001417 PMCID:PMC9602403

[157]

Thakur A,Zou H,Yang M.Inhibition of glioma cells’ proliferation by doxorubicin-loaded exosomes via microfluidics.Int J Nanomed2020;15:8331-43 PMCID:PMC7605152

[158]

Zhao Y,Li H.Biomaterial surface-mediated macrophages exert immunomodulatory roles by exosomal CCL2-induced membrane integrin β1 trafficking in recipient cells.Adv Sci2025;12:2409809 PMCID:PMC11905086

[159]

Chen J,Wan Y.Immune cell-derived exosomes as promising tools for cancer therapy.J Controlled Release2023;364:508-28

[160]

Wang W,Zhang D.USP5 inhibition via bone marrow-targeted engineered exosomes for myeloproliferative neoplasms therapy.J Nanobiotechnol2025;23:501 PMCID:PMC12247442

[161]

Yin Y,Li C.The status of industrialization and development of exosomes as a drug delivery system: a review.Front Pharmacol2022;13:961127 PMCID:PMC9592696

[162]

Nguyen VD,Choi YH,Choi E.Tumor-derived extracellular vesicles for the active targeting and effective treatment of colorectal tumors in vivo.Drug Deliv2022;29:2621-31 PMCID:PMC9367655

[163]

Zhan Q,Qi H.Engineering blood exosomes for tumor-targeting efficient gene/chemo combination therapy.Theranostics2020;10:7889-905 PMCID:PMC7359100

[164]

Jiang L,Du Y,Wu X.Engineering exosomes endowed with targeted delivery of triptolide for malignant melanoma therapy.ACS Appl Mater Interfaces2021;13:42411-28

[165]

Liu J,Li T.On the feasibility of SERS-based monitoring of drug loading efficiency in exosomes for targeted delivery.Biosensors2025;15:141 PMCID:PMC11939968

[166]

Wu J,Fu T.Extracellular vesicle-based drug delivery systems in cancer therapy.Int J Mol Sci2025;26:4835 PMCID:PMC12112466

[167]

Li Z,Ren Y,Su Z.Thermal-triggered loading and GSH-responsive releasing property of HBc particles for drug delivery.J Controlled Release2023;362:784-96

[168]

Alvarez-erviti L,Yin H,Lakhal S.Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes.Nat Biotechnol2011;29:341-5

[169]

Wang C,Li Y.Engineering a HEK-293T exosome-based delivery platform for efficient tumor-targeting chemotherapy/internal irradiation combination therapy.J Nanobiotechnol2022;20:247 PMCID:PMC9153154

[170]

Wu K,Chiang RY.CAP-LAMP2b-modified stem cells’ extracellular vesicles hybrid with CRISPR-Cas9 targeting ADAMTS4 to reverse IL-1β-induced aggrecan loss in chondrocytes.Int J Mol Sci2025;26:9812 PMCID:PMC12525490

[171]

Gu Y,Jiang L.αvβ3 integrin-specific exosomes engineered with cyclopeptide for targeted delivery of triptolide against malignant melanoma.J Nanobiotechnol2022;20:384 PMCID:PMC9400227

[172]

Kang C,Lee JS,Kim D.Anchor, spacer, and ligand-modified engineered exosomes for trackable targeted therapy.Bioconjugate Chem2020;31:2541-52

[173]

Tian Y,Song J.A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy.Biomaterials2014;35:2383-90

[174]

Tian J,Song D.Engineered exosome for drug delivery: recent development and clinical applications.Int J Nanomed2023;18:7923-40 PMCID:PMC10752020

[175]

Macdougall LJ,Kloxin AM.Design of synthetic extracellular matrices for probing breast cancer cell growth using robust cyctocompatible nucleophilic thiol-yne addition chemistry.Biomaterials2018;178:435-47 PMCID:PMC6699181

[176]

Lim GT,Han HS.Bioorthogonally surface-edited extracellular vesicles based on metabolic glycoengineering for CD44-mediated targeting of inflammatory diseases.J Extracell Vesicle2021;10:e12077 PMCID:PMC7953464

[177]

Aare M,Muthu M,Singh M.Genetically bio-engineered PD-L1 targeted exosomes for immunotherapy of resistant triple negative breast cancer.Drug Deliv Transl Res2025;16:693-710 PMCID:PMC12893402

[178]

Wang JS,Lin AY.Utilization of exosome-based therapies to augment anti-PD-1/PD-L1 therapies.J Immunother Cancer2025;13:e010603 PMCID:PMC12035427

[179]

Yin Z,Ma T.Mechanisms underlying low-clinical responses to PD-1/PD-L1 blocking antibodies in immunotherapy of cancer: a key role of exosomal PD-L1.J Immunother Cancer2021;9:e001698 PMCID:PMC7818841

[180]

Salunkhe S,Basak M,Mittal A.Surface functionalization of exosomes for target-specific delivery and in vivo imaging & tracking: strategies and significance.J Controlled Release2020;326:599-614

[181]

Bolaños K,Jara-Guajardo P.In vivo targeted delivery of extracellular vesicle-gold nanorod hybrids to metastatic melanoma lung tumors.Int J Nanomed2025;20:6983-98 PMCID:PMC12132528

[182]

Chen H,Li X.Adriamycin-loaded exosome with anti-CD20 aptamers selectively suppresses human CD20+ melanoma stem cells.Skin Res Technol2022;29:e13259 PMCID:PMC9838758

[183]

Li L,Guo Q.Exosome-liposome hybrid nanoparticle codelivery of TP and miR497 conspicuously overcomes chemoresistant ovarian cancer.J Nanobiotechnol2022;20:50 PMCID:PMC8787930

[184]

Xie Q,Chen W.Membrane fusogenic liposomes facilitate the production of immunostimulatory extracellular vesicles for enhanced cancer therapy.J Mater Chem B2025;13:7490-501

[185]

Lee Y.Engineered perfluorochemical cancer-derived exosomes loaded with indocyanine green and camptothecin provide targeted photochemotherapy for effective cancer treatment.Int J Nanomed2025;20:327-42 PMCID:PMC11725285

[186]

Ho MY,Xing B.Bacteria extracellular vesicle as nanopharmaceuticals for versatile biomedical potential.Nano Converg2024;11:28 PMCID:PMC11239649

[187]

Gao Y,Wu M.Photosensitive hybrid γδ-T exosomes for targeted cancer photoimmunotherapy.ACS Nano2025;19:4251-68 PMCID:PMC11803918

[188]

Zhang M,Liu L.Engineered exosomes from different sources for cancer-targeted therapy.Sig Transduct Target Ther2023;8:124 PMCID:PMC10017761

[189]

Hazekawa M,Hosokawa M.Development of an organ-directed exosome-based siRNA-carrier derived from autologous serum for lung metastases and testing in the B16/BL6 spontaneous lung metastasis model.Pharmaceutics2022;14:815 PMCID:PMC9025519

[190]

Santos NL,Reis PP,Andrade LNS.Extracellular vesicle-packaged miR-195-5p sensitizes melanoma to targeted therapy with kinase inhibitors.Cells2023;12:1317 PMCID:PMC10177607

[191]

Park JH,Jeon H.A novel convex acoustic lens-attached ultrasound drug delivery system and its testing in a murine melanoma subcutaneous model.Int J Pharm2023;642:123118

[192]

Duan M,Yi X.Doxorubicin delivery by pYEEIE peptide-functionalized rhodiola rosea-derived exosome-like nanovesicles for targeted melanoma therapy.Front Pharmacol2025;16:1619998 PMCID:PMC12336210

[193]

Lee JH,Kim IG.Exosome-mediated delivery of transforming growth factor-β receptor 1 kinase inhibitors and toll-like receptor 7/8 agonists for combination therapy of tumors.Acta Biomater2022;141:354-63

[194]

Huang C,Feng X,Li Y.Delivery of engineered primary tumor-derived exosomes effectively suppressed the colorectal cancer chemoresistance and liver metastasis.ACS Nano2023;17:10313-26

[195]

Ehexige E,Bazarjav P.Silencing of STAT3 via peptidomimetic LNP-mediated systemic delivery of RNAi downregulates PD-L1 and inhibits melanoma growth.Biomolecules2020;10:285 PMCID:PMC7072202

[196]

Faruqu FN,Xu L.Membrane radiolabelling of exosomes for comparative biodistribution analysis in immunocompetent and immunodeficient mice - a novel and universal approach.Theranostics2019;9:1666-82 PMCID:PMC6485196

[197]

Villa A,De Mitri Z.Preclinical pharmacology of patient-derived extracellular vesicles for the intraoperative imaging of tumors.Theranostics2024;14:6301-18 PMCID:PMC11488097

[198]

Sadeghi S,Tahmasebi S,Hashemi SM.Exosome engineering in cell therapy and drug delivery.Inflammopharmacology2023;31:145-69 PMCID:PMC9823267

[199]

Antimisiaris SG,Marazioti A.Exosomes and exosome-inspired vesicles for targeted drug delivery.Pharmaceutics2018;10:218 PMCID:PMC6321407

[200]

Kostyusheva A,Yan N,Zamyatnin AA.Breaking barriers in targeted therapy: advancing exosome Isolation, Engineering, and imaging.Adv Drug Delivery Rev2025;218:115522

[201]

Zhao S,Fan H.Targeted delivery of extracellular vesicles: the mechanisms, techniques and therapeutic applications.Mol Biomed2024;5:60 PMCID:PMC11579273

[202]

Hu M,Zhang X.Extracellular vesicles for targeted drug delivery: advances in surface modification strategies and therapeutic applications.J Transl Med2025;23:1028 PMCID:PMC12486671

[203]

Leary N,He Y.Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes.J Extracell Vesicle2022;11:e12197 PMCID:PMC8859913

[204]

Zhang W,Wang B.ICAM-1-mediated adhesion is a prerequisite for exosome-induced T cell suppression.Dev Cell2022;57:329-43.e7 PMCID:PMC8881799

[205]

Jackson Cullison SR,Karagoz K,Mahoney MG.Mechanisms of extracellular vesicle uptake and implications for the design of cancer therapeutics.J Extracell Bio2024;3:e70017 PMCID:PMC11522837

[206]

Song H,Hao Y,Xie Q.Nanoengineering facilitating the target mission: targeted extracellular vesicles delivery systems design.J Nanobiotechnol2022;20:431 PMCID:PMC9524104

[207]

Bader J,Leroux J.Extracellular vesicles versus lipid nanoparticles for the delivery of nucleic acids.Adv Drug Delivery Rev2024;215:115461

[208]

Gandek TB,Nagelkerke A.A comparison of cellular uptake mechanisms, delivery efficacy, and intracellular fate between liposomes and extracellular vesicles.Adv Healthc Mater2023;12:2300319 PMCID:PMC11469107

[209]

Nieuwland R.A beginner's guide to study extracellular vesicles in human blood plasma and serum.J Extracell Vesicle2024;13:e12400 PMCID:PMC10775135

[210]

György B,Balbisi M.Effect of the 35 nm and 70 nm size exclusion chromatography (SEC) column and plasma storage time on separated extracellular vesicles.Curr Issues Mol Biol2024;46:4337-57 PMCID:PMC11120626

[211]

Alter CL,Puligilla RD.Nano plasma membrane vesicle-lipid nanoparticle hybrids for enhanced gene delivery and expression.Adv Healthc Mater2024;14:2401888 PMCID:PMC11694093

[212]

Li Q,Shao J.Exploring regulatory frameworks for exosome therapy: insights and perspectives.Health Care Sci2025;4:299-309 PMCID:PMC12371722

[213]

Mizenko RR,Bozkurt BT.A critical systematic review of extracellular vesicle clinical trials.J Extracell Vesicle2024;13:e12510 PMCID:PMC11428870

[214]

Sun D,Xiang X.A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes.Mol Ther2010;18:1606-14 PMCID:PMC2956928

[215]

Wahlgren J,Brisslert M.Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes.Nucleic Acids Res2012;40:e130 PMCID:PMC3458529

[216]

Kim MS,Zhao Y.Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells.Nanomed Nanotechnol Biol Med2016;12:655-64 PMCID:PMC4809755

[217]

Guo P,Huang J,Moses MA.A facile magnetic extrusion method for preparing endosome-derived vesicles for cancer drug delivery.Adv Funct Mater2021;31:2008326 PMCID:PMC8680268

[218]

Ohno S,Sudo K.Systemically injected exosomes targeted to EGFR deliver antitumor MicroRNA to breast cancer cells.Mol Ther2013;21:185-91 PMCID:PMC3538304

[219]

Pham TC,Pham TT.Covalent conjugation of extracellular vesicles with peptides and nanobodies for targeted therapeutic delivery.J Extracell Vesicle2021;10:e12057 PMCID:PMC7886705

[220]

Smyth T,Payton NM.Surface functionalization of exosomes using click chemistry.Bioconjugate Chem2014;25:1777-84 PMCID:PMC4198107

[221]

Ferraz LS,Rodrigues T.Liquid biopsy as a potential tool for diagnosis and clinical monitoring of cutaneous and uveal melanoma.J Liquid Biopsy2025;9:100306 PMCID:PMC12205811

[222]

Uman S,Dominic J,Burdick JA.Comparison of technologies for manufacturing extracellular vesicles for therapeutic applications.Trends Biotechnol2026;44:1079-99 PMCID:PMC13179004

[223]

Javdani-Mallak A,Alibolandi M.Tumor-derived exosomes and their application in cancer treatment.J Transl Med2025;23:751 PMCID:PMC12236016

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