{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T13:07:53Z","timestamp":1788959273580,"version":"build-2803163510"},"reference-count":78,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Beijing Natural Science Foundation","award":["7244472"],"award-info":[{"award-number":["7244472"]}]},{"name":"Peking Union Medical College Hospital Talent Cultivation Program","award":["UHB12915"],"award-info":[{"award-number":["UHB12915"]}]},{"award":["UHB12915"],"award-info":[{"award-number":["UHB12915"]}],"id":[{"id":"https:\/\/ror.org\/04jztag35","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Peking Union Medical College Hospital Talent Cultivation Program","award":["UGG06314"],"award-info":[{"award-number":["UGG06314"]}]},{"award":["UGG06314"],"award-info":[{"award-number":["UGG06314"]}],"id":[{"id":"https:\/\/ror.org\/04jztag35","id-type":"ROR","asserted-by":"publisher"}]},{"name":"State Key Laboratory of Advanced Drug Delivery and Release Systems","award":["DSQZ-ZD-20250105"],"award-info":[{"award-number":["DSQZ-ZD-20250105"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>RNA therapeutics offer considerable potential for cancer treatment. Their therapeutic application, however, remains limited by rapid degradation, inefficient cellular uptake, and restricted intracellular release. Extracellular vesicles (EVs) are cell-derived membrane vesicles that have been exploited as promising vehicles for drug delivery due to their high biocompatibility and low immunogenicity, whereas liposomes and lipid nanoparticles provide tunable lipid composition and efficient loading of exogenous nucleic acids. Combining these carriers has led to EV\u2013lipid hybrid systems designed to integrate their complementary properties. This review summarizes recent advances in EV\u2013lipid hybrids for cancer therapy and organizes the reported systems according to their structural architecture and preparation. EV\u2013liposome fusion hybrids, EV\u2013lipid nanoparticle hybrids, and EV membrane-integrated lipid nanocarriers are discussed in relation to their RNA-loading strategies and representative therapeutic designs. The review also examines the key processes involved in functional RNA delivery and summarizes representative applications across different cancer types. Challenges associated with safety evaluation are also discussed, together with future directions for clinical translation. Overall, EV\u2013lipid hybrids represent a promising strategy for RNA-based cancer therapy.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091108","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T14:35:29Z","timestamp":1788359729000},"page":"1108","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extracellular Vesicle\u2013Lipid Hybrid Systems for RNA Delivery in Cancer: Structural Classification, Functional Delivery, and Translational Challenges"],"prefix":"10.3390","volume":"18","author":[{"given":"Lu","family":"Lu","sequence":"first","affiliation":[{"name":"<roman>Department of Pharmacy & State Key Laboratory of Complex Severe and Rare Disease<\/roman>, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"},{"name":"State Key Laboratory of Advanced Drug Delivery and Release Systems, Yantai 264003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yige","family":"Qiu","sequence":"additional","affiliation":[{"name":"<roman>Department of Pharmacy & State Key Laboratory of Complex Severe and Rare Disease<\/roman>, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Dou","sequence":"additional","affiliation":[{"name":"<roman>Department of Pharmacy & State Key Laboratory of Complex Severe and Rare Disease<\/roman>, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9050-9203","authenticated-orcid":false,"given":"Jing","family":"Yang","sequence":"additional","affiliation":[{"name":"Bioinformatics Center of AMMS, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2643-0706","authenticated-orcid":false,"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[{"name":"<roman>Department of Pharmacy & State Key Laboratory of Complex Severe and Rare Disease<\/roman>, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"108862","DOI":"10.1016\/j.biotechadv.2026.108862","article-title":"RNA therapeutics 2.0: Expanding the landscape from mRNA vaccines to splicing modulators and beyond","volume":"89","author":"Karwa","year":"2026","journal-title":"Biotechnol. Adv."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"126451","DOI":"10.1016\/j.ijpharm.2025.126451","article-title":"Nano\/micro-scale targeted RNA delivery systems for cancer therapy","volume":"688","author":"Li","year":"2026","journal-title":"Int. J. Pharm."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Monfaredan, A., \u015een, S., Fathi, N.K., Ta\u015ftekin, D., Hosseininasab, A., Bozbey, H.U., and \u00d6nc\u00fcl, O. (2025). Enhancing Antitumor Efficacy of MUC1 mRNA Nano-Vaccine by CTLA-4 siRNA-Mediated Immune Checkpoint Modulation in Triple Negative Breast Cancer Mice Model. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26178448"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.jconrel.2023.07.054","article-title":"Lipid nanoparticles for siRNA delivery in cancer treatment","volume":"361","author":"Garbayo","year":"2023","journal-title":"J. Control. Release"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Pandey, K., Jha, S., Chaliha, L.B., Gosai, H., and Patel, R. (2026). Nanomaterial-enabled RNA therapeutics: Bridging delivery barriers to clinical translation. Front. Nanotechnol., 8.","DOI":"10.3389\/fnano.2026.1860221"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2948","DOI":"10.1016\/j.fmre.2023.11.020","article-title":"Delivery of nucleic acid drugs for tumor therapy: Opportunities and challenges","volume":"5","author":"Sun","year":"2025","journal-title":"Fundam. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"8971","DOI":"10.1021\/acsnano.5c21857","article-title":"Mechanistic and Strategic Insights into How Lipid Nanoparticles Interact with Membrane-Based Biological Barriers","volume":"20","author":"Zhao","year":"2026","journal-title":"ACS Nano"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Szebeni, J. (2025). Unique Features and Collateral Immune Effects of mRNA-LNP COVID-19 Vaccines: Plausible Mechanisms of Adverse Events and Complications. Pharmaceutics, 17.","DOI":"10.20944\/preprints202501.1462.v1"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/s41580-020-0251-y","article-title":"RNA delivery by extracellular vesicles in mammalian cells and its applications","volume":"21","author":"Breyne","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e12404","DOI":"10.1002\/jev2.12404","article-title":"Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches","volume":"13","author":"Welsh","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"17802","DOI":"10.1021\/acsnano.2c08774","article-title":"Exosomes\u2014Nature\u2019s Lipid Nanoparticles, a Rising Star in Drug Delivery and Diagnostics","volume":"16","author":"Tenchov","year":"2022","journal-title":"ACS Nano"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1080\/14712598.2020.1738377","article-title":"Promising RNA-based cancer gene therapy using extracellular vesicles for drug delivery","volume":"20","author":"Xue","year":"2020","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1038\/s41401-022-00902-w","article-title":"Current advances in the use of exosomes, liposomes, and bioengineered hybrid nanovesicles in cancer detection and therapy","volume":"43","author":"Mukherjee","year":"2022","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"42658","DOI":"10.1021\/acsnano.5c16991","article-title":"Optimizing Exosome Lipid Hybrid Nanoparticles for Enhanced siRNA Delivery and Improved Therapeutic Anticancer Efficacy In Vivo","volume":"19","author":"Tandiono","year":"2025","journal-title":"ACS Nano"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2101202","DOI":"10.1002\/adhm.202101202","article-title":"Functional siRNA Delivery by Extracellular Vesicle\u2013Liposome Hybrid Nanoparticles","volume":"11","author":"Evers","year":"2022","journal-title":"Adv. Healthc. Mater."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"16652","DOI":"10.1039\/D4NR02191F","article-title":"Maximizing liposome tumor delivery by hybridizing with tumor-derived extracellular vesicles","volume":"16","author":"Sulthana","year":"2024","journal-title":"Nanoscale"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/s44222-026-00405-x","article-title":"The status of extracellular vesicles as drug carriers and therapeutics","volume":"4","author":"Chaudhari","year":"2026","journal-title":"Nat. Rev. Bioeng."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2005709","DOI":"10.1002\/adma.202005709","article-title":"Engineered Extracellular Vesicles for Cancer Therapy","volume":"33","author":"Zhang","year":"2021","journal-title":"Adv. Mater."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.jconrel.2024.08.017","article-title":"Development of an engineered extracellular vesicles-based vaccine platform for combined delivery of mRNA and protein to induce functional immunity","volume":"374","author":"Luo","year":"2024","journal-title":"J. Control. Release"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jconrel.2019.12.005","article-title":"Exosome-mediated siRNA delivery to suppress postoperative breast cancer metastasis","volume":"318","author":"Zhao","year":"2020","journal-title":"J. Control. Release"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e70673","DOI":"10.1002\/mco2.70673","article-title":"An Engineered Extracellular Vesicle With Enhanced Tumor and Lymph Nodes Targeting as siRNA Delivery System for Robust Tumor Immunotherapy","volume":"7","author":"Wang","year":"2026","journal-title":"MedComm"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2407619","DOI":"10.1002\/advs.202407619","article-title":"Novel Endogenous Engineering Platform for Robust Loading and Delivery of Functional mRNA by Extracellular Vesicles","volume":"11","author":"Zickler","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/s41565-017-0012-z","article-title":"Nanoparticle orientation to control RNA loading and ligand display on extracellular vesicles for cancer regression","volume":"13","author":"Pi","year":"2018","journal-title":"Nat. Nanotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"595161","DOI":"10.2147\/IJN.S595161","article-title":"Precision Engineering of Extracellular Vesicles as Programmable Carriers for mRNA Therapeutics","volume":"21","author":"Yoon","year":"2026","journal-title":"Int. J. Nanomed."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1038\/s41571-025-01074-2","article-title":"Clinical relevance of extracellular vesicles in cancer\u2014Therapeutic and diagnostic potential","volume":"22","author":"Greening","year":"2025","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.addr.2018.03.008","article-title":"Advances in microfluidics for lipid nanoparticles and extracellular vesicles and applications in drug delivery systems","volume":"128","author":"Maeki","year":"2018","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1038\/s41578-021-00358-0","article-title":"Lipid nanoparticles for mRNA delivery","volume":"6","author":"Hou","year":"2021","journal-title":"Nat. Rev. Mater."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4105","DOI":"10.1016\/j.apsb.2022.11.026","article-title":"Lipid carriers for mRNA delivery","volume":"13","author":"Zhang","year":"2023","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2001294","DOI":"10.1002\/adhm.202001294","article-title":"Environment-Responsive Lipid\/siRNA Nanoparticles for Cancer Therapy","volume":"10","author":"Lu","year":"2021","journal-title":"Adv. Healthc. Mater."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"102107","DOI":"10.1016\/j.mtbio.2025.102107","article-title":"Engineered lipid nanoparticles with synergistic dendritic cell targeting and enhanced endosomal escape for boosted mRNA cancer vaccines","volume":"34","author":"Wang","year":"2025","journal-title":"Mater. Today Bio"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5501","DOI":"10.1039\/D4NR05371K","article-title":"In vivo vectorization and delivery systems for gene therapies and RNA-based therapeutics in oncology","volume":"17","author":"Broekgaarden","year":"2025","journal-title":"Nanoscale"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1186\/s12951-022-01429-2","article-title":"Application of lipid nanovesicle drug delivery system in cancer immunotherapy","volume":"20","author":"Ding","year":"2022","journal-title":"J. Nanobiotechnology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5961","DOI":"10.1039\/D4CS00891J","article-title":"Engineered multi-domain lipid nanoparticles for targeted delivery","volume":"54","author":"Liu","year":"2025","journal-title":"Chem. Soc. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5905","DOI":"10.1039\/D5NA00323G","article-title":"Antibody-functionalized lipid nanocarriers for RNA-based cancer gene therapy: Advances and challenges in targeted delivery","volume":"7","author":"Nabih","year":"2025","journal-title":"Nanoscale Adv."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s13045-024-01574-1","article-title":"Lipid-based nanosystems: The next generation of cancer immune therapy","volume":"17","author":"Cheng","year":"2024","journal-title":"J. Hematol. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1080\/14686996.2019.1627174","article-title":"PEGylated liposomes: Immunological responses","volume":"20","author":"Mohamed","year":"2019","journal-title":"Sci. Technol. Adv. Mater."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"12410","DOI":"10.1021\/jacs.3c13123","article-title":"Programmable RNA Loading of Extracellular Vesicles with Toehold-Release Purification","volume":"146","author":"Malle","year":"2024","journal-title":"J. Am. Chem. Soc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s12951-022-01264-5","article-title":"Exosome-liposome hybrid nanoparticle codelivery of TP and miR497 conspicuously overcomes chemoresistant ovarian cancer","volume":"20","author":"Li","year":"2022","journal-title":"J. Nanobiotechnology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"11838","DOI":"10.1021\/acsnano.3c03050","article-title":"Therapeutic m6A Eraser ALKBH5 mRNA-Loaded Exosome\u2013Liposome Hybrid Nanoparticles Inhibit Progression of Colorectal Cancer in Preclinical Tumor Models","volume":"17","author":"Wu","year":"2023","journal-title":"ACS Nano"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"eadv6990","DOI":"10.1126\/sciadv.adv6990","article-title":"Engineering hybrid nanoparticles for targeted codelivery of triptolide and CYP3A4 -siRNA against pulmonary metastatic melanoma","volume":"11","author":"Gu","year":"2025","journal-title":"Sci. Adv."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"121723","DOI":"10.1016\/j.biomaterials.2022.121723","article-title":"Inhibition of SerpinB9 to enhance granzyme B-based tumor therapy by using a modified biomimetic nanoplatform with a cascade strategy","volume":"288","author":"Han","year":"2022","journal-title":"Biomaterials"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"102999","DOI":"10.1016\/j.mtbio.2026.102999","article-title":"An exosome-biomimetic photothermal nanocarrier for IGF2BP2 siRNA delivery and enhanced ferroptosis in head and neck squamous cell carcinoma","volume":"37","author":"Li","year":"2026","journal-title":"Mater. Today Bio"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"100845","DOI":"10.1016\/j.mtbio.2023.100845","article-title":"Extracellular vesicles hybrid plasmid-loaded lipid nanovesicles for synergistic cancer immunotherapy","volume":"23","author":"Tong","year":"2023","journal-title":"Mater. Today Bio"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"46705","DOI":"10.1021\/acsami.5c10385","article-title":"Ex Vivo High-Dose Ionizing Irradiation-Conditioned Nanovesicles for Enhancing the Immune Effects of Tumor Radiotherapy","volume":"17","author":"Yang","year":"2025","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"115642","DOI":"10.1016\/j.colsurfb.2026.115642","article-title":"Honeysuckle-derived vesicle-like nanoparticle and their hybrid vesicle as novel drug delivery systems for glioma therapy","volume":"264","author":"Liu","year":"2026","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"114745","DOI":"10.1016\/j.jconrel.2026.114745","article-title":"Losartan primes pancreatic tumors for effective exosome-biomimetic chemo-immunotherapy","volume":"393","author":"Hu","year":"2026","journal-title":"J. Control. Release"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e12198","DOI":"10.1002\/jev2.12198","article-title":"Tumour-derived extracellular vesicle membrane hybrid lipid nanovesicles enhance siRNA delivery by tumour-homing and intracellular freeway transportation","volume":"11","author":"Zhou","year":"2022","journal-title":"J. Extracell. Vesicles"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2100042","DOI":"10.1002\/mabi.202100042","article-title":"Phosphatidylcholine-Engineered Exosomes for Enhanced Tumor Cell Uptake and Intracellular Antitumor Drug Delivery","volume":"21","author":"Zhan","year":"2021","journal-title":"Macromol. Biosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e01195","DOI":"10.1002\/smtd.202501195","article-title":"Single-Particle Characterization Reveals Heterogeneous Extracellular Vesicle Fusion with Liposomes","volume":"10","author":"Mizenko","year":"2026","journal-title":"Small Methods"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"pgac156","DOI":"10.1093\/pnasnexus\/pgac156","article-title":"Extracellular vesicle fusion visualized by cryo-electron microscopy","volume":"1","author":"Morandi","year":"2022","journal-title":"PNAS Nexus"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1038\/s41596-019-0126-x","article-title":"Asymmetric-flow field-flow fractionation technology for exomere and small extracellular vesicle separation and characterization","volume":"14","author":"Zhang","year":"2019","journal-title":"Nat. Protoc."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/s41580-025-00922-4","article-title":"Biology and therapeutic potential of extracellular vesicle targeting and uptake","volume":"27","author":"Ripoll","year":"2026","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5612","DOI":"10.1021\/acs.analchem.1c00339","article-title":"Real-Time Luminescence Assay for Cytoplasmic Cargo Delivery of Extracellular Vesicles","volume":"93","author":"Somiya","year":"2021","journal-title":"Anal. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e12171","DOI":"10.1002\/jev2.12171","article-title":"Reporter gene assay for membrane fusion of extracellular vesicles","volume":"10","author":"Somiya","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1038\/nbt.2612","article-title":"Image-based analysis of lipid nanoparticle\u2013mediated siRNA delivery, intracellular trafficking and endosomal escape","volume":"31","author":"Gilleron","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1038\/nbt.3298","article-title":"Visualizing lipid-formulated siRNA release from endosomes and target gene knockdown","volume":"33","author":"Wittrup","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1038\/s41565-024-01785-0","article-title":"Direct cytosolic delivery of siRNA via cell membrane fusion using cholesterol-enriched exosomes","volume":"19","author":"Zhuo","year":"2024","journal-title":"Nat. Nanotechnol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s42003-021-01728-8","article-title":"A high-throughput Galectin-9 imaging assay for quantifying nanoparticle uptake, endosomal escape and functional RNA delivery","volume":"4","author":"Munson","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e202110137","DOI":"10.1083\/jcb.202110137","article-title":"Endosomal escape of delivered mRNA from endosomal recycling tubules visualized at the nanoscale","volume":"221","author":"Paramasivam","year":"2022","journal-title":"J. Cell Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5354","DOI":"10.1038\/s41467-025-60959-z","article-title":"Cellular and biophysical barriers to lipid nanoparticle mediated delivery of RNA to the cytosol","volume":"16","author":"Johansson","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1016\/S0140-6736(19)32319-0","article-title":"Colorectal cancer","volume":"394","author":"Dekker","year":"2019","journal-title":"Lancet"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1016\/S0140-6736(20)30974-0","article-title":"Pancreatic cancer","volume":"395","author":"Mizrahi","year":"2020","journal-title":"Lancet"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41572-020-00240-3","article-title":"Hepatocellular carcinoma","volume":"7","author":"Llovet","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/s41572-019-0111-2","article-title":"Breast cancer","volume":"5","author":"Harbeck","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1016\/S0140-6736(18)32552-2","article-title":"Epithelial ovarian cancer","volume":"393","author":"Lheureux","year":"2019","journal-title":"Lancet"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/S0140-6736(18)31559-9","article-title":"Melanoma","volume":"392","author":"Schadendorf","year":"2018","journal-title":"Lancet"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41572-020-00224-3","article-title":"Head and neck squamous cell carcinoma","volume":"6","author":"Johnson","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1093\/neuonc\/noaa106","article-title":"Glioblastoma in adults: A Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions","volume":"22","author":"Wen","year":"2020","journal-title":"Neuro-Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2403199","DOI":"10.1002\/adma.202403199","article-title":"Immunogenicity of Extracellular Vesicles","volume":"36","author":"Xia","year":"2024","journal-title":"Adv. Mater."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e59","DOI":"10.1002\/jex2.59","article-title":"Pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to Macaca nemestrina","volume":"1","author":"Driedonks","year":"2022","journal-title":"J. Extracell. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2583","DOI":"10.1111\/ajt.16591","article-title":"T cell antigenicity and immunogenicity of allogeneic exosomes","volume":"21","author":"Prunevieille","year":"2021","journal-title":"Am. J. Transplant."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1097\/MOH.0000000000000521","article-title":"Cancer cell-derived tissue factor-positive extracellular vesicles: Biomarkers of thrombosis and survival","volume":"26","author":"Hisada","year":"2019","journal-title":"Curr. Opin. Hematol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"6867","DOI":"10.1016\/j.biomaterials.2010.05.027","article-title":"The systemic toxicity of positively charged lipid nanoparticles and the role of Toll-like receptor 4 in immune activation","volume":"31","author":"Kedmi","year":"2010","journal-title":"Biomaterials"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2312026","DOI":"10.1002\/adma.202312026","article-title":"Physicochemical Targeting of Lipid Nanoparticles to the Lungs Induces Clotting: Mechanisms and Solutions","volume":"36","author":"Zamora","year":"2024","journal-title":"Adv. Mater."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1007\/s11095-024-03757-4","article-title":"Quality and Safety Considerations for Therapeutic Products Based on Extracellular Vesicles","volume":"41","author":"Takakura","year":"2024","journal-title":"Pharm. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"30087","DOI":"10.3402\/jev.v4.30087","article-title":"Applying extracellular vesicles based therapeutics in clinical trials\u2014An ISEV position paper","volume":"4","author":"Lener","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"114001","DOI":"10.1016\/j.addr.2021.114001","article-title":"Development of extracellular vesicle-based medicinal products: A position paper of the group \u2018Extracellular Vesicle translatiOn to clinicaL perspectiVEs\u2014EVOLVE France\u2019","volume":"179","author":"Silva","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"8696","DOI":"10.1038\/s41467-025-63718-2","article-title":"Engineered exosomes with KrasG12D specific siRNA in pancreatic cancer: A phase I study with immunological correlates","volume":"16","author":"Kalluri","year":"2025","journal-title":"Nat. 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