Engineered Extracellular Vesicles: Advancing Cancer Therapy Through Precision Nanomedicine

Abstract

Extracellular vesicles (EVs) are nanoscale membrane structures secreted by cells that contain proteins, nucleic acids, and lipids, and reflect the physiologic state of the parent cells. EVs have a critical role in intercellular communication, signal transduction, and tumorigenesis, influencing tumor progression, metastasis, and remodeling of the tumor microenvironment. Recent advances have highlighted the potential of EVs as natural nanocarriers for cancer therapy that offer advantages, such as biocompatibility, low immunogenicity, and the ability to cross biological barriers. Engineered EVs may overcome many of the limitations of natural EVs, including the low yield, heterogeneity, and limited targeting capabilities. Engineered EVs have shown promise in preclinical studies through genetic engineering, surface modification, and optimized loading strategies in the delivery of therapeutic agents, such as CRISPR/Cas9, mRNA, siRNA, and drugs with enhanced precision and efficacy. EVs loaded with CRISPR/Cas9 plasmids targeting PARP-1 have been shown to induce apoptosis in ovarian cancer cells and increase the sensitivity to cisplatin. Engineered EVs expressing PD-1/PD-L1 blocking antibodies have demonstrated potent anti-tumor immune activity in melanoma models by reactivating exhausted T cells, highlighting the potential for use in cancer immunotherapy. These EVs have been studied in preclinical settings involving targeted therapy, immunotherapy, and combination therapies, such as chemo-photothermal approaches, with the potential to overcoming multidrug resistance and improving treatment outcomes. Despite the promise of EVs, challenges remain in large-scale production, purification, and standardization. Corollary studies are warranted to optimize EV engineering, enhance safety, and evaluate the potential for clinical translation in oncology.

Keywords

Cancer nanomedicine / engineered EVs / extracellular vesicles / targeted drug delivery / tumor microenvironment

References

[1] Santucci C, Carioli G, Bertuccio P, Malvezzi M, Pastorino U, et al. Progress in cancer mortality, incidence, and survival: a global overview. Eur J Cancer Prev 2020; 29(5): 367-81. [PMID: 32740162 DOI: 10.1097/cej.0000000000000594]

[2] Casolino R, Tatah L, Charnaud S, Santero M, Ilbawi A, et al. The WHO global landscape of cancer clinical trials. Nat Med 2025; 31(9): 2901-12. [PMID: 40926101 DOI: 10.1038/s41591-025-03926-x]

[3] Liu B, Zhou H, Tan L, Siu KTH, Guan XY. Exploring treatment options in cancer: tumor treatment strategies. Signal Transduct Target Ther 2024; 9(1): 175. [PMID: 39013849 DOI: 10.1038/s41392-024-01856-7]

[4] Chen Y, Du M, Yu J, Rao L, Chen X, et al. Nanobiohybrids: a synergistic integration of bacteria and nanomaterials in cancer therapy. BIOI 2020; 1(1): 25-36. [DOI: 10.15212/bioi-2020-0008]

[5] Zhou G, Zhou Q, Li R, Sheng S, Gao Q, et al. Synthetically engineered bacterial extracellular vesicles and IL-4-encapsulated hydrogels sequentially promote osteoporotic fracture repair. ACS Nano 2025; 19(16): 16064-83. [PMID: 40237831 DOI: 10.1021/acsnano.5c03106]

[6] Liu H, Song P, Zhang H, Zhou F, Ji N, et al. Synthetic biology-based bacterial extracellular vesicles displaying BMP-2 and CXCR4 to ameliorate osteoporosis. J Extracell Vesicles 2024; 13(4): e12429. [PMID: 38576241 DOI: 10.1002/jev2.12429]

[7] Liu H, Wu Y, Wang F, Wang S, Ning J, et al. Bone-targeted engineered bacterial extracellular vesicles delivering miRNA to treat osteoporosis. Compos Part B Eng 2023; 267: 111047. [DOI: 10.1016/j.compositesb.2023.111047]

[8] Qian L, Chen P, Zhang S, Wang Z, Guo Y, et al. The uptake of extracellular vesicles: research progress in cancer drug resistance and beyond. Drug Resist Updat 2025; 79: 101209. [PMID: 39893749 DOI: 10.1016/j.drup.2025.101209]

[9] Han R, Zhou D, Ji N, Yin Z, Wang J, et al. Folic acid-modified ginger-derived extracellular vesicles for targeted treatment of rheumatoid arthritis by remodeling immune microenvironment via the PI3K-AKT pathway. J Nanobiotechnology 2025; 23(1): 41. [PMID: 39849554 DOI: 10.1186/s12951-025-03096-5]

[10] Bai M, Li Z, Shi T, Li X, Li J, et al. Exogenous extracellular vesicles as emerging platforms in translational medicine. BIO Integration 2025; 6: 1-25. [DOI: 10.15212/bioi-2025-0122]

[11] Wu W, Deng Z, Liu X, Yang Y, Yuan H, et al. Engineered N1 neutrophil-derived vesicles for photothermal-enhanced immunochemotherapy of esophageal cancer. Nano Res 2025; 18(10): 94907965. [DOI: 10.26599/nr.2025.94907965]

[12] Ji N, Wang F, Wang M, Zhang W, Liu H, et al. Engineered bacterial extracellular vesicles for central nervous system diseases. J Control Release 2023; 364: 46-60. [PMID: 40237831 DOI: 10.1021/acsnano.5c03106]

[13] Luo T, Fan Z, Zeng A, Wang A, Pan Y, et al. Biomimetic targeted co-delivery system engineered from genomic insights for precision treatment of osteosarcoma. Adv Sci (Weinh). 2025; 12(2): e2410427. [PMID: 39555699 DOI: 10.1002/advs.202410427]

[14] Jeppesen DK, Zhang Q, Franklin JL, Coffey RJ. Extracellular vesicles and nanoparticles: emerging complexities. Trends Cell Biol 2023; 33(8): 667-81. [PMID: 3673775 DOI: 10.1016/j.tcb.2023.01.002]

[15] Yu J, Sane S, Kim JE, Yun S, Kim HJ, et al. Biogenesis and delivery of extracellular vesicles: harnessing the power of EVs for diagnostics and therapeutics. Front Mol Biosci 2023; 10: 1330400. [PMID: 38234582 DOI: 10.3389/fmolb.2023.1330400]

[16] Zhou X, Huang J, Zhang D, Qian Z, Zuo X, et al. Small extracellular vesicles: the origins, current status, future prospects, and applications. Stem Cell Res Ther 2025; 16(1): 184. [PMID: 40247402 DOI: 10.1186/s13287-025-04330-5]

[17] Guo W, Li Y, Pang W, Shen H. Exosomes: a potential therapeutic tool targeting communications between tumor cells and macrophages. Mol Ther 2020; 28(9): 1953-64. [PMID: 32563274 DOI: 10.1016/j.ymthe.2020.06.003]

[18] Ashoub MH, Salavatipour MS, Kasgari FH, Valandani HM, Khalilabadi RM. Extracellular microvesicles: biologic properties, biogenesis, and applications in leukemia. Mol Cell Biochem 2024; 479(2): 419-30. [PMID: 37084166 DOI: 10.1007/s11010-023-04734-y]

[19] Ou Q, Huang W, Wang B, Niu L, Li Z, et al. Apoptotic vesicles: therapeutic mechanisms and critical issues. J Dent Res 2024; 103(11): 1057-65. [PMID: 39282215 DOI: 10.1177/00220345241265676]

[20] Sun B, Li R, Ji N, Liu H, Wang H, et al. Brain-targeting drug delivery systems: the state of the art in treatment of glioblastoma. Mater Today Bio 2025; 30: 101443. [PMID: 39866779 DOI: 10.1016/j.mtbio.2025.101443]

[21] Fyfe J, Casari I, Manfredi M, Falasca M. Role of lipid signalling in extracellular vesicles-mediated cell-to-cell communication. Cytokine Growth Factor Rev 2023; 73: 20-6. [PMID: 37648617 DOI: 10.1016/j.cytogfr.2023.08.006]

[22] Kalluri R. The biology and function of extracellular vesicles in immune response and immunity. Immunity 2024; 57(8): 1752-68. [PMID: 39142276 DOI: 10.1016/j.immuni.2024.07.009]

[23] Wang Y, Zhao M, Liu S, Guo J, Lu Y, et al. Macrophage-derived extracellular vesicles: diverse mediators of pathology and therapeutics in multiple diseases. Cell Death Dis 2020; 11(10): 924. [PMID: 33116121 DOI: 10.1038/s41419-020-03127-z]

[24] Kopec M, Abramczyk H. The role of pro- and antiangiogenic factors in angiogenesis process by Raman spectroscopy. Spectrochim Acta A Mol Biomol Spectrosc 2022; 268: 120667. [PMID: 34865975 DOI: 10.1016/j.saa.2021.120667]

[25] Galassi C, Chan TA, Vitale I, Galluzzi L. The hallmarks of cancer immune evasion. Cancer Cell 2024; 42(11): 1825-63. [PMID: 39393356 DOI: 10.1016/j.ccell.2024.09.010]

[26] Zhou G, Li R, Sheng S, Huang J, Zhou F, et al. Organoids and organoid extracellular vesicles-based disease treatment strategies. J Nanobiotechnology 2024; 22(1): 679. [PMID: 39506799 DOI: 10.1186/s12951-024-02917-3]

[27] Park J, Kim H, Roh YH, Ko J. Advances in single extracellular vesicle characterization and multiplexed profiling. TrAC Trends Anal Chem 2026; 195: 118588. [DOI: 10.1016/j.trac.2025.118588]

[28] Ye Z, Li G, Lei J. Influencing immunity: role of extracellular vesicles in tumor immune checkpoint dynamics. Exp Mol Med 2024; 56(11): 2365-81. [PMID: 39528800 DOI: 10.1038/s12276-024-01340-w]

[29] Banjade S, Zhu L, Jorgensen JR, Suzuki SW, Emr SD. Recruitment and organization of ESCRT-0 and ubiquitinated cargo via condensation. Sci Adv 2022; 8(13): eabm5149. [PMID: 35363519 DOI: 10.1126/sciadv.abm5149]

[30] Peche VS, Pietka TA, Jacome-Sosa M, Samovski D, Palacios H, et al. Endothelial cell CD36 regulates membrane ceramide formation, exosome fatty acid transfer and circulating fatty acid levels. Nat Commun 2023; 14(1): 4029. [PMID: 37419919 DOI: 10.1038/s41467-023-39752-3]

[31] Bae JW, Yi JK, Jeong EJ, Lee WJ, Hwang JM, et al. Ras-related proteins (Rab) play significant roles in sperm motility and capacitation status. Reprod Biol 2022; 22(2): 100617. [PMID: 35180567 DOI: 10.1016/j.repbio.2022.100617]

[32] Elsharkasy OM, Nordin JZ, Hagey DW, de Jong OG, Schiffelers RM, et al. Extracellular vesicles as drug delivery systems: why and how? Adv Drug Deliv Rev 2020; 159: 332-43. [PMID: 32305351 DOI: 10.1016/j.addr.2020.04.004]

[33] Kwok ZH, Wang C, Jin Y. Extracellular vesicle transportation and uptake by recipient cells: a critical process to regulate human diseases. Processes (Basel) 2021; 9(2): 273. [PMID: 34336602 DOI: 10.3390/pr9020273]

[34] Li S, Li W, Wu X, Zhang B, Liu L, et al. Immune cell-derived extracellular vesicles for precision therapy of inflammatory-related diseases. J Control Release 2024; 368: 533-47. [PMID: 38462043 DOI: 10.1016/j.jconrel.2024.03.007]

[35] Zheng W, He R, Liang X, Roudi S, Bost J, et al. Cell-specific targeting of extracellular vesicles through engineering the glycocalyx. J Extracell Vesicles 2022; 11(12): e12290. [PMID: 36463392 DOI: 10.1002/jev2.12290]

[36] de Jong B, Barros ER, Hoenderop JGJ, Rigalli JP. Recent advances in extracellular vesicles as drug delivery systems and their potential in precision medicine. Pharmaceutics 2020; 12(11): 1006. [PMID: 33105857 DOI: 10.3390/pharmaceutics12111006]

[37] Cheng HY, Su GL, Wu YX, Chen G, Yu ZL, et al. Extracellular vesicles in anti-tumor drug resistance: mechanisms and therapeutic prospects. J Pharm Anal 2024; 14(7): 100920. [PMID: 39104866 DOI: 10.1016/j.jpha.2023.12.010]

[38] Sabani B, Brand M, Albert I, Inderbitzin J, Eichenseher F, et al. A novel surface functionalization platform to prime extracellular vesicles for targeted therapy and diagnostic imaging. Nanomedicine 2023; 47: 102607. [PMID: 36167305 DOI: 10.1016/j.nano.2022.102607]

[39] Sánchez GB, Bunn KE, Pua HH, Rafat M. Extracellular vesicles: mediators of intercellular communication in tissue injury and disease. Cell Commun Signal 2021; 19(1): 104. [PMID: 34656117 DOI: 10.1186/s12964-021-00787-y]

[40] Skotland T, Sagini K, Sandvig K, Llorente A. An emerging focus on lipids in extracellular vesicles. Adv Drug Deliv Rev 2020; 159: 308-21. [PMID: 32151658 DOI: 10.1016/j.addr.2020.03.002]

[41] Kang T, Atukorala I, Mathivanan S. Biogenesis of extracellular vesicles. Subcell Biochem 2021; 97: 19-43. [PMID: 33779912 DOI: 10.1007/978-3-030-67171-6_2]

[42] Nemeth K, Bayraktar R, Ferracin M, Calin GA. Non-coding RNAs in disease: from mechanisms to therapeutics. Nat Rev Genet 2024; 25(3): 211-32. [PMID: 37968332 DOI: 10.1038/s41576-023-00662-1]

[43] Li M, Liao L, Tian W. Extracellular vesicles derived from apoptotic cells: an essential link between death and regeneration. Front Cell Dev Biol 2020; 8: 573511. [PMID: 33134295 DOI: 10.3389/fcell.2020.573511]

[44] Huang K, Xu Y, Feng T, Lan H, Ling F, et al. The advancement and application of the single-cell transcriptome in biological and medical research. Biology (Basel) 2024; 13(6): 451. [PMID: 38927331 DOI: 10.3390/biology13060451]

[45] Zhang X, Tang J, Kou X, Huang W, Zhu Y, et al. Proteomic analysis of MSC-derived apoptotic vesicles identifies Fas inheritance to ameliorate haemophilia a via activating platelet functions. J Extracell Vesicles 2022; 11(7): e12240. [PMID: 36856683 DOI: 10.1002/jev2.12240]

[46] Liu A, Peng P, Wei C, Meng F, Huang X, et al. Apoptotic vesicles derived from mesenchymal stem cells ameliorate hypersensitivity responses via inducing CD8⁺ T cells apoptosis with calcium overload and mitochondrial dysfunction. Adv Sci (Weinh) 2025; 12(22): e2407446. [PMID: 40089865 DOI: 10.1002/advs.202407446]

[47] Xu F, Jiang D, Xu J, Dai H, Fan Q, et al. Engineering of dendritic cell bispecific extracellular vesicles for tumor-targeting immunotherapy. Cell Rep 2023; 42(10): 113138. [PMID: 37738123 DOI: 10.1016/j.celrep.2023.113138]

[48] Kooijmans SAA, de Jong OG, Schiffelers RM, Schiffelers RM. Exploring interactions between extracellular vesicles and cells for innovative drug delivery system design. Adv Drug Deliv Rev 2021; 173: 252-78. [PMID: 33798644 DOI: 10.1016/j.addr.2021.03.017]

[49] Karmacharya M, Kumar S, Cho YK. Tuning the extracellular vesicles membrane through fusion for biomedical applications. J Funct Biomater 2023; 14(2): 117. [PMID: 36826916 DOI: 10.3390/jfb14020117]

[50] Ginini L, Billan S, Fridman E, Gil Z. Insight into extracellular vesicle-cell communication: from cell recognition to intracellular fate. Cells 2022; 11(9): 1375. [PMID: 35563681 DOI: 10.3390/cells11091375]

[51] Wang X, Yang X, Huang C, Liu T, Zang H, et al. Tumor-derived extracellular vesicle PD-1 promotes tumor immune evasion via disruption of peripheral T cell homeostasis. Cancer Lett 2025; 612: 217486. [PMID: 39864541 DOI: 10.1016/j.canlet.2025.217486]

[52] Bebelman MP, Smit MJ, Pegtel DM, Baglio SR. Biogenesis and function of extracellular vesicles in cancer. Pharmacol Ther 2018; 188: 1-11. [PMID: 29476772 DOI: 10.1016/j.pharmthera.2018.02.013]

[53] Lugano R, Ramachandran M, Dimberg A. Tumor angiogenesis: causes, consequences, challenges and opportunities. Cell Mol Life Sci 2020; 77(9): 1745-70. [PMID: 31690961 DOI: 10.1007/s00018-019-03351-7]

[54] Zhang S, Yang J, Shen L. Extracellular vesicle-mediated regulation of tumor angiogenesis-implications for anti-angiogenesis therapy. J Cell Mol Med 2021; 25(6): 2776-85. [PMID: 33586248 DOI: 10.1111/jcmm.16359]

[55] Bao Q, Huang Q, Chen Y, Wang Q, Sang R, et al. Tumor-derived extracellular vesicles regulate cancer progression in the tumor microenvironment. Front Mol Biosci 2021; 8: 796385. [PMID: 35059436 DOI: 10.3389/fmolb.2021.796385]

[56] Lehmann BD, Paine MS, Brooks AM, McCubrey JA, Renegar RH, et al. Senescence-associated exosome release from human prostate cancer cells. Cancer Res 2008; 68(19): 7864-71. [PMID: 18829542 DOI: 10.1158/0008-5472.Can-07-6538]

[57] Takasugi M, Okada R, Takahashi A, Virya Chen D, Watanabe S, et al. Small extracellular vesicles secreted from senescent cells promote cancer cell proliferation through EphA2. Nat Commun 2017; 8: 15728. [PMID: 28585531 DOI: 10.1038/ncomms15728]

[58] Pavlyukov MS, Yu H, Bastola S, Minata M, Shender VO, et al. Apoptotic cell-derived extracellular vesicles promote malignancy of glioblastoma via intercellular transfer of splicing factors. Cancer Cell 2018; 34(1): 119-35.e10. [PMID: 29937354 DOI: 10.1016/j.ccell.2018.05.012]

[59] Yang L, Wu XH, Wang D, Luo CL, Chen LX. Bladder cancer cell-derived exosomes inhibit tumor cell apoptosis and induce cell proliferation in vitro. Mol Med Rep 2013; 8(4): 1272- 8. [PMID: 23969721 DOI: 10.3892/mmr.2013.1634]

[60] Branco H, Xavier CPR, Riganti C, Vasconcelos MH. Hypoxia as a critical player in extracellular vesicles-mediated intercellular communication between tumor cells and their surrounding microenvironment. Biochim Biophys Acta (BBA) - Rev Cancer 2025; 1880: 189244. [PMID: 39672279 DOI: 10.1016/j.bbcan.2024.189244]

[61] Chang WH, Cerione RA, Antonyak MA. Extracellular vesicles and their roles in cancer progression. Methods Mol Biol 2021; 2174: 143-70. [PMID: 32813249 DOI: 10.1007/978-1-0716-0759-6_10]

[62] Singh S, Chen CC, Kim S, Singh A, Singh G. Role of extracellular vesicle microRNAs and RNA binding proteins on glioblastoma dynamics and therapeutics development. Extracell Vesicle 2024; 4: 100049. [DOI: 10.1016/j.vesic.2024.100049]

[63] Apostolou S, Donega V. Embracing the heterogeneity of neural stem cells in the subventricular zone. Stem Cell Reports 2025; 20(9): 102452. [PMID: 40118056 DOI: 10.1016/j.stemcr.2025.102452]

[64] Zhao S, Umpierre AD, Wu LJ. Tuning neural circuits and behaviors by microglia in the adult brain. Trends Neurosci 2024; 47(3): 181-94. [PMID: 38245380 DOI: 10.1016/j.tins.2023.12.003]

[65] Xiao Y, Wang SK, Zhang Y, Rostami A, Kenkare A, et al. Role of extracellular vesicles in neurodegenerative diseases. Prog Neurobiol 2021; 201: 102022. [PMID: 33617919 DOI: 10.1016/j.pneurobio.2021.102022]

[66] Jezierzański M, Nafalska N, Stopyra M, Furgoł T, Miciak M, et al. Temozolomide (TMZ) in the treatment of glioblastoma multiforme-a literature review and clinical outcomes. Curr Oncol 2024; 31(7): 3994-4002. [PMID: 39057168 DOI: 10.3390/curroncol31070296]

[67] Ma S, Lu Y, Sui S, Yang JS, Fu BB, et al. Unraveling the triad of immunotherapy, tumor microenvironment, and skeletal muscle biomechanics in oncology. Front Immunol 2025; 16: 1572821. [PMID: 40242775 DOI: 10.3389/fimmu.2025.1572821]

[68] Chung WM, Molony RD, Lee YF. Non-stem bladder cancer cell-derived extracellular vesicles promote cancer stem cell survival in response to chemotherapy. Stem Cell Res Ther 2021; 12(1): 533. [PMID: 34627375 DOI: 10.1186/s13287-021-02600-6]

[69] Benmelouka AY, Munir M, Sayed A, Attia MS, Ali MM, et al. Neural stem cell-based therapies and glioblastoma management: current evidence and clinical challenges. Int J Mol Sci 2021; 22(5): 2258. [PMID: 33668356 DOI: 10.3390/ijms22052258]

[70] Zeng A, Wei Z, Rabinovsky R, Jun HJ, El Fatimy R, et al. Glioblastoma-derived extracellular vesicles facilitate transformation of astrocytes via reprogramming oncogenic metabolism. iScience 2020; 23(8): 101420. [PMID: 32795915 DOI: 10.1016/j.isci.2020.101420]

[71] Fattahi E, Kankam SB, Khoshnevisan A, Hashemi AP. Evaluating prognosis and survival in patients with glioblastoma in contact with subventricular zone: tumor location and its correlation with prognosis. Med J Armed Forces India 2024; 80(Suppl 1): S21-8. [PMID: 39734827 DOI: 10.1016/j.mjafi.2022.06.012]

[72] Mendt M, Kamerkar S, Sugimoto H, McAndrews KM, Wu CC, et al. Generation and testing of clinical-grade exosomes for pancreatic cancer. JCI Insight 2018; 3(8): e99263. [PMID: 29669940 DOI: 10.1172/jci.insight.99263]

[73] Luo X, McAndrews KM, Kalluri R. Natural and bioengineered extracellular vesicles in diagnosis, monitoring and treatment of cancer. ACS Nano 2025; 19(6): 5871-96. [PMID: 39869032 DOI: 10.1021/acsnano.4c11630]

[74] Hu M, Han Y, Zhang X, Tian S, Shang Z, et al. Extracellular vesicles for targeted drug delivery: advances in surface modification strategies and therapeutic applications. J Transl Med 2025; 23(1): 1028. [PMID: 41029680 DOI: 10.1186/s12967-025-07077-y]

[75] Patel N, LaMastro V, Giblin J, Avery E, Noor B, et al. Genetically engineering cells to produce therapeutically boosted extracellular vesicles for cardiovascular calcification. Biomaterials 2026; 325: 123552. [PMID: 40682948 DOI: 10.1016/j.biomaterials.2025.123552]

[76] Ye C, Ma Y, Shrestha R, Cai J, Liu Y, et al. Extracellular vesicle-mediated delivery of CRISPR machinery silences androgen receptor in castration-resistant prostate cancer cells. Mol Ther 2026; 34(1): 281-99. [PMID: 41017153 DOI: 10.1016/j.ymthe.2025.09.045]

[77] Park KC, Jaafari AM, Smith CA, Lobo AR, Errichelli L, et al. A Langendorff-heart discovery pipeline demonstrates cardiomyocyte targeting by extracellular vesicles functionalized with beta-blockers using click-chemistry. J MolCell Cardiol 2025; 204: 89-100. [PMID: 40414416 DOI: 10.1016/j.yjmcc.2025.05.007]

[78] Sato Y, Zhang W, Baba T, Chung UI, Teramura Y. Extracellular vesicle-liposome hybrids via membrane fusion using cell-penetrating peptide-conjugated lipids. Regen Ther 2024; 26: 533-40. [PMID: 39165408 DOI: 10.1016/j.reth.2024.07.006]

[79] Dave KM, Pinky PP, Manickam DS. Molecular engineering of extracellular vesicles for drug delivery: strategies, challenges, and perspectives. J Control Release 2025; 386: 114068. [PMID: 40721069 DOI: 10.1016/j.jconrel.2025.114068]

[80] Zhang T, Liu Z, Wei Y, Lu J, He Z, et al. Extracellular vesicles as natural nanocarriers: from in vitro engineering to in situ generation in cancer therapy. Chem Eng J 2025; 510: 161653. [DOI: 10.1016/j.cej.2025.161653]

[81] Ding L, Zhang T, Pan Y, Liu J, Ma T, et al. Extracellular vesicles in chronic wound therapy: engineering strategies and advanced delivery systems for enhanced regeneration. Mater Today Bio 2025; 35: 102298. [PMID: 41890412 DOI: 10.1016/j.mtbio.2025.102298]

[82] Mediratta K, Diab MD, Han P, Hu H, Wang L. Emerging strategies for cargo loading and engineering of extracellular vesicles for breast cancer treatment. Nanomaterials (Basel) 2025; 15(18): 1418. [PMID: 41003053 DOI: 10.3390/nano15181418]

[83] Liu Y, Xiang C, Dai Y, Li C, Okeke MN, et al. Engineered apoptotic vesicle mimetics with tunable “eat-me” signaling precisely regulate tumor-associated macrophages for potentiating cancer immunotherapy. Acta Pharm Sin B 2025. [DOI: 10.1016/j.apsb.2025.11.032]

[84] Zhang K, Fang J. Extracellular vesicles in drug delivery: from quality assurance to therapeutic application. Int J Nanomedicine 2026; 21: 579695. [DOI: 10.2147/IJN.S579695]

[85] Zhao C, Wang Z, Kim H, Kong H, Lee J, et al. Identification of tumor-specific surface proteins enables quantification of extracellular vesicle subtypes for early detection of pancreatic ductal adenocarcinoma. Adv Sci (Weinh) 2025; 12(21): e2414982. [PMID: 40130819 DOI: 10.1002/advs.202414982]

[86] Omarini C, Catani V, Mastrolia I, Toss A, Banchelli F, et al. Extracellular vesicles-derived miR-21 as a biomarker for early diagnosis and tumor activity in breast cancer subtypes. Biomark Res 2025; 13(1): 14. [PMID: 39849610 DOI: 10.1186/s40364-025-00724-y]

[87] Ma S, Zhao N, Dong X, Wang Y, Song L, et al. Liquid biopsy-derived extracellular vesicle protein biomarkers for diagnosis and prognostic assessment of lung squamous cell carcinoma. Cancer Cell Int 2025; 25(1): 161. [PMID: 40275246 DOI: 10.1186/s12935-025-03792-0]

[88] Li LY, Liang SY, Cai MP, Ge JC, Tan HS, et al. Engineered extracellular vesicles as imaging biomarkers and therapeutic applications for urological diseases. Mater Today Bio 2025; 32: 101646. [PMID: 40160248 DOI: 10.1016/j.mtbio.2025.101646]

[89] Gao C, Zhao W, Feng R, Zhang L, Ge L, et al. Melanin nanoparticles-loaded lactobacillus fermentum exosomes for targeted and visualized treatment of ulcerative colitis. J Adv Res 2025; 82: 1049-67. [PMID: 40555281 DOI: 10.1016/j.jare.2025.06.068]

[90] Sun JX, Xia QD, Xu JZ, An Y, Ma SY, et al. A novel prostate cancer-specific fluorescent probe based on extracellular vesicles targeting STEAP1 applied in fluorescence guided surgery. J Control Release 2025; 380: 199-218. [PMID: 39894263 DOI: 10.1016/j.jconrel.2025.01.079]

[91] Yousefli Z, Rafiee N, Nourollahian T, Alipour A, Haghshenas Z, et al. Recent advances of circulating biomarkers with potential diagnostic, prognostic, and therapeutic value in pancreatic cancer: limitations of clinical application. Pathol Res Pract 2025; 272: 156045. [PMID: 40483840 DOI: 10.1016/j.prp.2025.156045]

[92] Jiang H, Kumarasamy RV, Pei J, Raju KRS, Kanniappan GV, et al. Integrating engineered nanomaterials with extracellular vesicles: advancing targeted drug delivery and biomedical applications. Front Nanotechnol 2025; 6: 1513683. [DOI: 10.3389/fnano.2024.1513683]

[93] Ma S, Dang D, Wang W, Wang Y, Liu L. Concentration optimization of combinatorial drugs using Markov chain-based models. BMC Bioinformatics 2021; 22(1): 451. [PMID: 34548014 DOI: 10.1186/s12859-021-04364-5]

[94] Ma S, Wu J, Liu Z, He R, Wang Y, et al. Quantitative characterization of cell physiological state based on dynamical cell mechanics for drug efficacy indication. J Pharm Anal 2023; 13(4): 388-402. [PMID: 37181289 DOI: 10.1016/j.jpha.2023.03.002]

[95] Kim SM, Yang Y, Oh SJ, Hong Y, Seo M, et al. Cancer-derived exosomes as a delivery platform of CRISPR/Cas9 confer cancer cell tropism-dependent targeting. J Control Release 2017; 266: 8-16. [PMID: 28916446 DOI: 10.1016/j.jconrel.2017.09.013]

[96] El Andaloussi S, Mäger I, Breakefield XO, Wood MJ. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov 2013; 12(5): 347-57. [PMID: 23584393 DOI: 10.1038/nrd3978]

[97] Yang Z, Shi J, Xie J, Wang Y, Sun J, et al. Large-scale generation of functional mRNA-encapsulating exosomes via cellular nanoporation. Nat Biomed Eng 2020; 4(1): 69-83. [PMID: 31844155 DOI: 10.1038/s41551-019-0485-1]

[98] Xiao K, Lai Y, Yuan W, Li S, Liu X, et al. mRNA-based chimeric antigen receptor T cell therapy: basic principles, recent advances and future directions. Interdiscip Med 2024; 2(1): e20230036. [DOI: 10.1002/INMD.20230036]

[99] Wang JH, Forterre AV, Zhao J, Frimannsson DO, Delcayre A, et al. Anti-HER2 scFv-directed extracellular vesicle-mediated mRNA-based gene delivery inhibits growth of HER2-positive human breast tumor xenografts by prodrug activation. Mol Cancer Ther 2018; 17(5): 1133-42. [PMID: 29483213 DOI: 10.1158/1535-7163.Mct-17-0827]

[100] Pi F, Binzel DW, Lee TJ, Li Z, Sun M, et al. Nanoparticle orientation to control RNA loading and ligand display on extracellular vesicles for cancer regression. Nat Nanotechnol 2018; 13(1): 82-9. [PMID: 29230043 DOI: 10.1038/s41565-017-0012-z]

[101] Zhang H, Wang J, Ren T, Huang Y, Liang X, et al. Bone marrow mesenchymal stem cell-derived exosomal miR-206 inhibits osteosarcoma progression by targeting TRA2B. Cancer Lett 2020; 490: 54-65. [PMID: 32682951 DOI: 10.1016/j.canlet.2020.07.008]

[102] Nie H, Xie X, Zhang D, Zhou Y, Li B, et al. Use of lung-specific exosomes for miRNA-126 delivery in non-small cell lung cancer. Nanoscale 2020; 12(2): 877-87. [PMID: 31833519 DOI: 10.1039/c9nr09011h]

[103] Katakowski M, Buller B, Zheng X, Lu Y, Rogers T, et al. Exosomes from marrow stromal cells expressing miR-146b inhibit glioma growth. Cancer Lett 2013; 335(1): 201-4. [PMID: 23419525 DOI: 10.1016/j.canlet.2013.02.019]

[104] Ohno S, Takanashi M, Sudo K, Ueda S, Ishikawa A, et al. Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol Ther 2013; 21(1): 185-91. [PMID: 23032975 DOI: 10.1038/mt.2012.180]

[105] Choi H, Choi Y, Yim HY, Mirzaaghasi A, Yoo JK, et al. Biodistribution of exosomes and engineering strategies for targeted delivery of therapeutic exosomes. Tissue Eng Regen Med 2021; 18(4): 499-511. [PMID: 34260047 DOI: 10.1007/s13770-021-00361-0]

[106] Agrawal AK, Aqil F, Jeyabalan J, Spencer WA, Beck J, et al. Milk-derived exosomes for oral delivery of paclitaxel. Nanomedicine 2017; 13(5): 1627-36. [PMID: 28300659 DOI: 10.1016/j.nano.2017.03.001]

[107] Kim MS, Haney MJ, Zhao Y, Mahajan V, Deygen I, et al. Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomedicine 2016; 12(3): 655-64. [PMID: 26586551 DOI: 10.1016/j.nano.2015.10.012]

[108] Yuan Z, Kolluri KK, Gowers KH, Janes SM. TRAIL delivery by MSC-derived extracellular vesicles is an effective anticancer therapy. J Extracell Vesicles 2017; 6(1): 1265291. [PMID: 28326166 DOI: 10.1080/20013078.2017.1265291]

[109] Li J, Li J, Peng Y, Du Y, Yang Z, et al. Dendritic cell derived exosomes loaded neoantigens for personalized cancer immunotherapies. J Control Release 2023; 353: 423-33. [PMID: 36470333 DOI: 10.1016/j.jconrel.2022.11.053]

[110] Tsering T, Nadeau A, Wu T, Dickinson K, Burnier JV . Extracellular vesicle-associated DNA: ten years since its discovery in human blood. Cell Death Dis 2024; 15(9): 668. [PMID: 39266560 DOI: 10.1038/s41419-024-07003-y]

[111] Ding N, Daci A, Krasniqi V, Butler R, Goddard A, et al. Engineered extracellular vesicles demonstrate altered endocytosis and biodistribution and have superior oral siRNA delivery efficiency compared to lipid nanoparticles. Int J Pharm X 2025; 10: 100428. [PMID: 41256914 DOI: 10.1016/j.ijpx.2025.100428]

[112] Chen Y, Liang S, Peng Y, Ma K, Yun K, et al. Nanomaterials-enabled mRNA delivery for cancer immunotherapy. Coord Chem Rev 2025; 543: 216945. [DOI: 10.1016/j.ccr.2025]

[113] Balaraman AK, Arockia Babu M, Afzal M, Sanghvi G, Rekha MM, et al. Exosome-based miRNA delivery: transforming cancer treatment with mesenchymal stem cells. Regen Ther 2025; 28: 558-72. [PMID: 40034540 DOI: 10.1016/j.reth.2025.01.019]

[114] Al-Khafaji MK, Rahbarizadeh F, Ahmadvand D. Oligoclonal anti-HER2 nanobody-targeted exosomes as a nano carrier for doxorubicin delivery to HER2-positive breast cancer in vitro and in vivo. Int J Biol Macromol 2025; 333(Pt 2): 148626. [PMID: 41213374 DOI: 10.1016/j.ijbiomac.2025.148626]

[115] Deng L, Zhang H, Zhang Y, Luo S, Du Z, et al. An exosome-mimicking membrane hybrid nanoplatform for targeted treatment toward Kras-mutant pancreatic carcinoma. Biomater Sci 2021; 9(16): 5599-611. [PMID: 34250995 DOI: 10.1039/d1bm00446h]

[116] Cheng Q, Shi X, Han M, Smbatyan G, Lenz HJ, et al. Reprogramming exosomes as nanoscale controllers of cellular immunity. J Am Chem Soc 2018; 140(48): 16413-7. [PMID: 30452238 DOI: 10.1021/jacs.8b10047]

[117] Shi X, Cheng Q, Hou T, Han M, Smbatyan G, et al. Genetically engineered cell-derived nanoparticles for targeted breast cancer immunotherapy. Mol Ther 2020; 28(2): 536-47. [PMID: 31843452 DOI: 10.1016/j.ymthe.2019.11.020]

[118] Wan C, Sun Y, Tian Y, Lu L, Dai X, et al. Irradiated tumor cell-derived microparticles mediate tumor eradication via cell killing and immune reprogramming. Sci Adv 2020; 6(13): eaay9789. [PMID: 32232155 DOI: 10.1126/sciadv.aay9789]

[119] Lin W, Xu Y, Chen X, Liu J, Weng Y, et al. Radiation-induced small extracellular vesicles as “carriages” promote tumor antigen release and trigger antitumor immunity. Theranostics 2020; 10(11): 4871-84. [PMID: 32308755 DOI: 10.7150/thno.43539]

[120] Wang ZH, Peng WB, Zhang P, Yang XP, Zhou Q. Lactate in the tumour microenvironment: from immune modulation to therapy. EBioMedicine 2021; 73: 103627. [PMID: 34656878 DOI: 10.1016/j.ebiom.2021.103627]

[121] Nguyen Cao TG, Kang JH, Kim W, Lim J, Kang S, et al. Engineered extracellular vesicle-based sonotheranostics for dual stimuli-sensitive drug release and photoacoustic imaging-guided chemo-sonodynamic cancer therapy. Theranostics 2022; 12(3): 1247-66. [PMID: 35154485 DOI: 10.7150/thno.65516]

[122] Peng X, Peng Q, Wu M, Wang W, Gao Y, et al. A pH and temperature dual-responsive microgel-embedded, adhesive, and tough hydrogel for drug delivery and wound healing. ACS Appl Mater Interfaces 2023; 15(15): 19560-73. [PMID: 37036950 DOI: 10.1021/acsami.2c21255]

[123] Chen W, Li Y, Liu C, Kang Y, Qin D, et al. In situ engineering of tumor-associated macrophages via a nanodrug-delivering-drug (β-Elemene@Stanene) strategy for enhanced cancer chemo-immunotherapy. Angew Chem Int Ed Engl 2023; 62(41): e202308413. [PMID: 37380606 DOI: 10.1002/anie.202308413]

[124] Cao Y, Wu T, Zhang K, Meng X, Dai W, et al. Engineered exosome-mediated near-infrared-II region V₂C quantum dot delivery for nucleus-target low-temperature photothermal therapy. ACS Nano 2019; 13(2): 1499-510. [PMID: 30677286 DOI: 10.1021/acsnano.8b07224]

[125] Wen Z, Jiang L, Yu F, Xu X, Chen M, et al. scRNA-seq reveals NAMPT-mediated macrophage polarization shapes smooth muscle cell plasticity in pulmonary arterial hypertension. Interdiscip Med 2024; 2(4): e20240016. [DOI: 10.1002/INMD.20240016]

[126] Naseri M, Bozorgmehr M, Zöller M, Ranaei Pirmardan E, Madjd Z. Tumor-derived exosomes: the next generation of promising cell-free vaccines in cancer immunotherapy. Oncoimmunology 2020; 9(1): 1779991. [PMID: 32934883 DOI: 10.1080/2162402x.2020.1779991]

[127] Gardiner C, Di Vizio D, Sahoo S, Théry C, Witwer KW, et al. Techniques used for the isolation and characterization of extracellular vesicles: results of a worldwide survey. J Extracell Vesicles 2016; 5(1): 32945. [PMID: 27802845 DOI: 10.3402/jev.v5.32945]

[128] Liang G, Zhu Y, Ali DJ, Tian T, Xu H, 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(1): 10. [PMID: 31918721 DOI: 10.1186/s12951-019-0563-2]

[129] Zhang X, Zhang H, Gu J, Zhang J, Shi H, et al. Engineered extracellular vesicles for cancer therapy. Adv Mater 2021; 33(14): e2005709. [PMID: 33644908 DOI: 10.1002/adma.202005709]

[130] Gruenberg J, Maxfield FR. Membrane transport in the endocytic pathway. Curr Opin Cell Biol 1995; 7(4): 552-63. [PMID: 7495576 DOI: 10.1016/0955-0674(95)80013-1]

[131] Gudbergsson JM, Jønsson K, Simonsen JB, Johnsen KB. Systematic review of targeted extracellular vesicles for drug delivery - considerations on methodological and biological heterogeneity. J Control Release 2019; 306: 108-20. [PMID: 31175896 DOI: 10.1016/j.jconrel.2019.06.006]

[132] Gulati M, Grover M, Singh S, Singh M. Lipophilic drug derivatives in liposomes. Int J Pharm 1998; 165(2): 129-68. [DOI: 10.1016/S0378-5173(98)00006-4]

[133] Guo M, Wu F, Hu G, Chen L, Xu J, et al. Autologous tumor cell-derived microparticle-based targeted chemotherapy in lung cancer patients with malignant pleural effusion. Sci Transl Med 2019; 11(474): eaat5690. [PMID: 30626714 DOI: 10.1126/scitranslmed.aat5690]

[134] Haney MJ, Klyachko NL, Zhao Y, Gupta R, Plotnikova EG, et al. Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J Control Release 2015; 207: 18-30. [PMID: 25836593 DOI: 10.1016/j.jconrel.2015.03.033]

[135] Sayyed AA, Gondaliya P, Mali M, Pawar A, Bhat P, et al. MiR-155 inhibitor-laden exosomes reverse resistance to cisplatin in a 3D tumor spheroid and xenograft model of oral cancer. Mol Pharm 2021; 18(8): 3010-25. [PMID: 34176265 DOI: 10.1021/acs.molpharmaceut.1c00213]

[136] Haraszti RA, Miller R, Stoppato M, Sere YY, Coles A, et al. Exosomes produced from 3D cultures of MSCs by tangential flow filtration show higher yield and improved activity. Mol Ther 2018; 26(12): 2838-47. [PMID: 30341012 DOI: 10.1016/j.ymthe.2018.09.015]

[137] Xia P, Yuan H, Tian M, Zhong T, Hou R, et al. Surface-engineered extracellular vesicles with CDH17 nanobodies to efficiently deliver imaging probes and chemo-photothermal drugs for gastric cancer theragnostic. Adv Funct Mater 2022; 33: 2209393. [DOI: 10.1002/adfm.202209393]

[138] Wang D, Yao Y, He J, Zhong X, Li B, et al. Engineered cell-derived microparticles Bi₂Se₃/DOX@MPs for imaging guided synergistic photothermal/low-dose chemotherapy of cancer. Adv Sci 2019; 7(3): 1901293. [PMID: 32042550 DOI: 10.1002/advs.201901293]

[139] Yang K, Ren D, Wang Z, Dong Q, Xu M, et al. Apoptotic bodies encapsulating Ti₂N nanosheets for synergistic chemo-photothermal therapy. Nanotechnology 2024; 35(36): 365703. [PMID: 38861968 DOI: 10.1088/1361-6528/ad5690]

[140] Zhang D, Qin X, Wu T, Qiao Q, Song Q, et al. Extracellular vesicles based self-grown gold nanopopcorn for combinatorial chemo-photothermal therapy. Biomaterials 2019; 197: 220-8. [PMID: 30669014 DOI: 10.1016/j.biomaterials.2019.01.024]

[141] Tian R, Wang Z, Niu R, Wang H, Guan W, et al. Tumor exosome mimicking nanoparticles for tumor combinatorial chemo-photothermal therapy. Front Bioeng Biotechnol 2020; 8: 1010. [PMID: 32984284 DOI: 10.3389/fbioe.2020.01010]

[142] Zhu Y, Li W, Lan F, Chen S, Chen X, et al. DNA nanotechnology in tumor liquid biopsy: enrichment and determination of circulating biomarkers. Interdiscip Med 2024; 2(1): e20230043. [DOI: 10.1002/INMD.20230043]

[143] Zhu L, Dong D, Yu ZL, Zhao YF, Pang DW, et al. Folate-engineered microvesicles for enhanced target and synergistic therapy toward breast cancer. ACS Appl Mater Interfaces 2017; 9(6): 5100-8. [PMID: 28106372 DOI: 10.1021/acsami.6b14633]

[144] Wang C, Guan W, Peng J, Chen Y, Xu G, et al. Gene/paclitaxel co-delivering nanocarriers prepared by framework-induced self-assembly for the inhibition of highly drug-resistant tumors. Acta Biomater 2020; 103: 247-58. [PMID: 31846802 DOI: 10.1016/j.actbio.2019.12.015]

[145] Zhan Q, Yi K, Qi H, Li S, Li X, et al. Engineering blood exosomes for tumor-targeting efficient gene/chemo combination therapy. Theranostics 2020; 10(17): 7889-905. [PMID: 32685027 DOI: 10.7150/thno.45028]

[146] Baby HM, Zhang H, Selvadoss A, Pathrikar TV, Bajpayee AG. Rational design of extracellular vesicles for targeted drug delivery across physiological barriers. Nano Today 2026; 66: 102920. [DOI: 10.1016/j.nantod.2025.102920]

[147] Du X, Chen S, Meng T, Liu L, Li L, et al. Extracellular vesicles as precision therapeutic vectors: charting the future of cell-targeted therapies. Precis Med Eng 2025; 2(2): 100031. [DOI: 10.1016/j.preme.2025.100031]

[148] Li Q, Chen X, Xie J, Nie S. Engineered bacterial extracellular vesicles: developments, challenges, and opportunities. Engineering 2025; 54: 291-307. [DOI: 10.1016/j.eng.2025.06.042]

[149] Bader J, Brigger F, Leroux JC. Extracellular vesicles versus lipid nanoparticles for the delivery of nucleic acids. Adv Drug Deliv Rev 2024; 215: 115461. [PMID: 39490384 DOI: 10.1016/j.addr.2024.115461]

[150] Popowski KD, Moatti A, Scull G, Silkstone D, Lutz H, et al. Inhalable dry powder mRNA vaccines based on extracellular vesicles. Matter 2022; 5(9): 2960-74. [PMID: 35847197 DOI: 10.1016/j.matt.2022.06.012]

[151] Li Q, Xing H, Naeem A, Zhang K, Zheng A, et al. Extracellular vesicle-based mRNA therapeutics and vaccines. Exploration (Beijing) 2025; 5(6): 2240109. [PMID: 41476648 DOI: 10.1002/exp.20240109]

[152] Liang X, Gupta D, Xie J, Van Wonterghem E, Van Hoecke L, et al. Engineering of extracellular vesicles for efficient intracellular delivery of multimodal therapeutics including genome editors. Nat Commun 2025; 16(1): 4028. [PMID: 40301355 DOI: 10.1038/s41467-025-59377-y]

[153] Wang SM, Wang D, Shen YQ, Wang MH, Jia F, et al. Isolation and detection strategies for decoding the heterogeneity of extracellular vesicles. Chem Eng J 2025; 507: 160234. [DOI: 10.1016/j.cej.2025.160234]

[154] Picchio V, Pontecorvi V, Dhori X, Bordin A, Floris E, et al. The emerging role of artificial intelligence applied to exosome analysis: from cancer biology to other biomedical fields. Life Sci 2025; 375: 123752. [PMID: 40409585 DOI: 10.1016/j.lfs.2025.123752]

[155] Liu H, Geng Z, Su J. Engineered mammalian and bacterial extracellular vesicles as promising nanocarriers for targeted therapy. Extracell Vesicles Circ Nucl Acids 2022; 3(2): 63-86. [PMID: 39698442 DOI: 10.20517/evcna.2022.04]

[156] Chen H, Li Q. Recent advances in scalable exosome production: challenges and innovations. Chin J Plast Reconstr Surg 2025; 7(3): 149-63. [DOI: 10.1016/j.cjprs.2025.05.001]

[157] Zhong H, Mao Z, Li X, Deng A, Zhu Y, et al. A microfluidic device integrating magnetic stirring with tangential flow for high-efficiency isolation of small extracellular vesicles. Sens Actuators B Chem 2026; 447(Pt 2): 138898. [DOI: 10.1016/j.snb.2025.138898]

[158] Chen X, Liu X, Zhang C, Xia H, Qin X, et al. Isolation and detection of exosomes on microfluidic chips. Biomedical Instrumentation 2025; 1(1): 100007. [DOI: 10.1016/j.bmi.2025.100007]

[159] Ahn SH, Ryu SW, Choi H, You S, Park J, et al. Manufacturing therapeutic exosomes: from bench to industry. Mol Cells 2022; 45(5): 284-90. [PMID: 35534190 DOI: 10.14348/molcells.2022.2033]

[160] Mukerjee N, Bhattacharya A, Maitra S, Kaur M, Ganesan S, et al. Exosome isolation and characterization for advanced diagnostic and therapeutic applications. Mater Today Bio 2025; 31: 101613. [PMID: 40161926 DOI: 10.1016/j.mtbio.2025.101613]

[161] Jay SM. Addressing barriers to clinical translation of extracellular vesicle therapeutics. Mol Ther 2025; 33(5): 1879-80. [PMID: 40010335 DOI: 10.1016/j.ymthe.2025.02.020]

[162] Scharbert L, Strodel B. Innovative strategies for modeling peptide-protein interactions and rational peptide drug design. Curr Opin Struct Biol 2025; 93: 103083. [PMID: 40570517 DOI: 10.1016/j.sbi.2025.103083]

[163] Wen M, Wang J, Ou Z, Nie G, Chen Y, et al. Bacterial extracellular vesicles: a position paper by the microbial vesicles task force of the Chinese society for extracellular vesicles. Interdiscip Med 2023; 1(3): e20230017. [DOI: 10.1002/INMD.20230017]

[164] Liu H, Zhang H, Han Y, Hu Y, Geng Z, et al. Bacterial extracellular vesicles-based therapeutic strategies for bone and soft tissue tumors therapy. Theranostics 2022; 12(15): 6576-94. [PMID: 36185613 DOI: 10.7150/thno.78034]

[165] Kang J, Wen J, Chen H, Zhu C, Bai Y. Progress of research on engineered extracellular vesicles from different sources for disease treatment. Histol Histopathol 2025; 40(10): 1501-18. [PMID: 40134377 DOI: 10.14670/HH-18-903]

[166] Fu P, Guo Y, Luo Y, Mak M, Zhang J, et al. Visualization of microRNA therapy in cancers delivered by small extracellular vesicles. J Nanobiotechnology 2023; 21(1): 457. [PMID: 38031152 DOI: 10.1186/s12951-023-02187-5]

[167] Zheng W, Zhu T, Tang L, Li Z, Jiang G, et al. Inhalable CAR-T cell-derived exosomes as paclitaxel carriers for treating lung cancer. J Transl Med 2023; 21(1): 383. [PMID: 37308954 DOI: 10.1186/s12967-023-04206-3]

[168] Liu X, Liu X, Luo X, Zhu M, Liu N, et al. Synergistic strategies for glioblastoma treatment: CRISPR-based multigene editing combined with immune checkpoint blockade. J Nanobiotechnology 2025; 23(1): 94. [PMID: 39920725 DOI: 10.1186/s12951-025-03112-8]

[169] Wu Y, Chen W, Deng J, Cao X, Yang Z, et al. Tumour-derived microparticles obtained through microwave irradiation induce immunogenic cell death in lung adenocarcinoma. Nat Nanotechnol 2025; 20(8): 1119-30. [PMID: 40389640 DOI: 10.1038/s41565-025-01922-3]

[170] Yang G, Li Z, Usman R, Liu Y, Li S, et al. From biogenesis to aptasensors: advancements in analysis for tumor-derived extracellular vesicles research. Theranostics 2024; 14(10): 4161-83. [PMID: 38994022 DOI: 10.7150/thno.95885]

[171] Kanada M, Kim BD, Hardy JW, Ronald JA, Bachmann MH, et al. Microvesicle-mediated delivery of minicircle DNA results in effective gene-directed enzyme prodrug cancer therapy. Mol Cancer Ther 2019; 18(12): 2331-42. [PMID: 31451563 DOI: 10.1158/1535-7163.Mct-19-0299]

[172] Mizrak A, Bolukbasi MF, Ozdener GB, Brenner GJ, Madlener S, et al. Genetically engineered microvesicles carrying suicide mRNA/protein inhibit schwannoma tumor growth. Mol Ther 2013; 21(1): 101-8. [PMID: 22910294 DOI: 10.1038/mt.2012.161]

[173] Zhao L, Gu C, Gan Y, Shao L, Chen H, et al. Exosome-mediated siRNA delivery to suppress postoperative breast cancer metastasis. J Control Release 2020; 318: 1-15. [PMID: 31830541 DOI: 10.1016/j.jconrel.2019.12.005]

[174] Kim G, Kim M, Lee Y, Byun JW, Hwang DW, et al. Systemic delivery of microRNA-21 antisense oligonucleotides to the brain using T7-peptide decorated exosomes. J Control Release 2020; 317: 273-81. [PMID: 31730913 DOI: 10.1016/j.jconrel.2019.11.009]

[175] Wang X, Zhang H, Bai M, Ning T, Ge S, et al. Exosomes serve as nanoparticles to deliver anti-miR-214 to reverse chemoresistance to cisplatin in gastric cancer. Mol Ther 2018; 26(3): 774-83. [PMID: 29456019 DOI: 10.1016/j.ymthe.2018.01.001]

[176] Erkan EP, Senfter D, Madlener S, Jungwirth G, Ströbel T, et al. Extracellular vesicle-mediated suicide mRNA/protein delivery inhibits glioblastoma tumor growth in vivo. Cancer Gene Ther 2017; 24(1): 38-44. [PMID: 27982017 DOI: 10.1038/cgt.2016.78]

[177] Cheng G, Li W, Ha L, Han X, Hao S, et al. Self-assembly of extracellular vesicle-like metal-organic framework nanoparticles for protection and intracellular delivery of biofunctional proteins. J Am Chem Soc 2018; 140(23): 7282-91. [PMID: 29809001 DOI: 10.1021/jacs.8b03584]

[178] Nie W, Wu G, Zhang J, Huang LL, Ding J, et al. Responsive exosome nano-bioconjugates for synergistic cancer therapy. Angew Chem Int Ed Engl 2020; 59(5): 2018-22. [PMID: 31746532 DOI: 10.1002/anie.201912524]

[179] Fan M, Liu H, Yan H, Che R, Jin Y, et al. A CAR T-inspiring platform based on antibody-engineered exosomes from antigen-feeding dendritic cells for precise solid tumor therapy. Biomaterials 2022; 282: 121424. [PMID: 35196606 DOI: 10.1016/j.biomaterials.2022.121424]

[180] Wang G, Hu W, Chen H, Shou X, Ye T, et al. Cocktail strategy based on NK cell-derived exosomes and their biomimetic nanoparticles for dual tumor therapy. Cancers (Basel) 2019; 11(10): 1560. [PMID: 31615145 DOI: 10.3390/cancers11101560]

[181] Yong T, Zhang X, Bie N, Zhang H, Zhang X, et al. Tumor exosome-based nanoparticles are efficient drug carriers for chemotherapy. Nat Commun 2019; 10(1): 3838. [PMID: 31444335 DOI: 10.1038/s41467-019-11718-4]

[182] Gong C, Tian J, Wang Z, Gao Y, Wu X, et al. Functional exosome-mediated co-delivery of doxorubicin and hydrophobically modified microRNA 159 for triple-negative breast cancer therapy. J Nanobiotechnology 2019; 17(1): 93. [PMID: 31481080 DOI: 10.1186/s12951-019-0526-7]

[183] Liu X, Zhang G, Yu T, Liu J, Chai X, 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. [PMID: 37544559 DOI: 10.1016/j.ijbiomac.2023.126147]

[184] Zhang H, Wu B, Wang Y, Du H, Fang L. Extracellular vesicles as mediators and potential targets in combating cancer drug resistance. Molecules 2025; 30(3): 498. [PMID: 39942602 DOI: 10.3390/molecules30030498]

[185] Qiu Y, Sun J, Qiu J, Chen G, Wang X, et al. Antitumor activity of cabazitaxel and MSC-TRAIL derived extracellular vesicles in drug-resistant oral squamous cell carcinoma. Cancer Manag Res 2020; 12: 10809-20. [PMID: 33149686 DOI: 10.2147/cmar.S277324]

[186] Zhu L, Wang C, Pang DW, Zhang ZL. Controlled release of therapeutic agents with near-infrared laser for synergistic photochemotherapy toward cervical cancer. Anal Chem 2019; 91(10): 6555-60. [PMID: 30994332 DOI: 10.1021/acs.analchem.8b05982]

[187] Kim S, Kang JH, Nguyen Cao TG, Kang SJ, Jeong K, et al. Extracellular vesicles with high dual drug loading for safe and efficient combination chemo-phototherapy. Biomater Sci 2022; 10(11): 2817-30. [PMID: 35384946 DOI: 10.1039/d1bm02005f]

[188] Chen M, Sun Y, Liu H. Cell membrane biomimetic nanomedicines for cancer phototherapy. Interdisciplinary Medicine 2023; 1(2): e20220012. [DOI: 10.1002/INMD.20220012]

[189] Huang GT, Gronthos S, Shi S. Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine. J Dent Res 2009; 88(9): 792-806. [PMID: 19767575 DOI: 10.1177/0022034509340867]

[190] Jiang Z, Guan J, Qian J, Zhan C. Peptide ligand-mediated targeted drug delivery of nanomedicines. Biomater Sci 2019; 7(2): 461-71. [PMID: 30656305 DOI: 10.1039/c8bm01340c]

[191] Bellavia D, Raimondo S, Calabrese G, Forte S, Cristaldi M, et al. Interleukin 3- receptor targeted exosomes inhibit in vitro and in vivo Chronic Myelogenous Leukemia cell growth. Theranostics 2017; 7(5): 1333-45. [PMID: 28435469 DOI: 10.7150/thno.17092]

[192] Usman WM, Pham TC, Kwok YY, Vu LT, Ma V, et al. Efficient RNA drug delivery using red blood cell extracellular vesicles. Nat Commun 2018; 9(1): 2359. [PMID: 29907766 DOI: 10.1038/s41467-018-04791-8]

[193] Wang X, Mao K, Zhang X, Zhang Y, Yang YG, et al. Red blood cell derived nanocarrier drug delivery system: a promising strategy for tumor therapy. Interdiscip Med 2024; 2(3): e20240014. [DOI: 10.1002/INMD.20240014]

[194] Yang Y, Wang X, Wang M, Xiang Z, Li X, et al. Dual genes manipulation enhanced chemotherapy potentiates antitumor immunity based on extracellular vesicle system for glioblastoma treatment. Chem Eng J 2024; 500: 156638. [DOI: 10.1016/j.cej.2024.156638]