Engineered EVs designed to target diseases of the CNS

Engelhardt, 2009, The blood-brain and the blood-cerebrospinal fluid barriers: function and dysfunction, Semin. Immunopathol., 31, 497, 10.1007/s00281-009-0177-0 Turk, 2021, Delivery strategies for cell-based therapies in the brain: overcoming multiple barriers, Drug Deliv. Transl. Res., 11, 2448, 10.1007/s13346-021-01079-1 Bruzzone, 2006, Structure and function of gap junctions in the developing brain, Cell Tissue Res., 326, 239, 10.1007/s00441-006-0287-0 Gurke, 2008, The art of cellular communication: tunneling nanotubes bridge the divide, Histochem. Cell Biol., 129, 539, 10.1007/s00418-008-0412-0 Pokutta, 2002, The cytoplasmic face of cell contact sites, Curr. Opin. Struct. Biol., 12, 255, 10.1016/S0959-440X(02)00318-4 Genazzani, 2002, Hormonal influence on the central nervous system, Maturitas, 43, S11, 10.1016/S0378-5122(02)00144-5 Bucher, 2015, Electrochemical analysis of neurotransmitters, Annu Rev Anal Chem (Palo Alto, Calif), 8, 239, 10.1146/annurev-anchem-071114-040426 Araque, 2014, Gliotransmitters travel in time and space, Neuron, 81, 728, 10.1016/j.neuron.2014.02.007 Praznik, 2022, Regulation of protein secretion through chemical regulation of endoplasmic reticulum retention signal cleavage, Nat. Commun., 13, 1323, 10.1038/s41467-022-28971-9 Zappulli, 2016, Extracellular vesicles and intercellular communication within the nervous system, J. Clin. Invest., 126, 1198, 10.1172/JCI81134 Hill, 2019, Extracellular vesicles and neurodegenerative diseases, J. Neurosci., 39, 9269, 10.1523/JNEUROSCI.0147-18.2019 Thery, 2018, Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines, J. Extracell. Vesicles, 7, 1535750, 10.1080/20013078.2018.1535750 Abels, 2016, Introduction to extracellular vesicles: biogenesis, RNA cargo selection, content, release, and uptake, Cell. Mol. Neurobiol., 36, 301, 10.1007/s10571-016-0366-z Zhang, 2021, Immunomagnetic sequential ultrafiltration (iSUF) platform for enrichment and purification of extracellular vesicles from biofluids, Sci. Rep., 11, 8034, 10.1038/s41598-021-86910-y Rufino-Ramos, 2017, Extracellular vesicles: novel promising delivery systems for therapy of brain diseases, J. Control. Release, 262, 247, 10.1016/j.jconrel.2017.07.001 Shi, 2019, New windows into the brain: central nervous system-derived extracellular vesicles in blood, Prog. Neurobiol., 175, 96, 10.1016/j.pneurobio.2019.01.005 Figueroa, 2018, Detection of glioblastoma in biofluids, J. Neurosurg., 129, 334, 10.3171/2017.3.JNS162280 Banks, 2020, Transport of extracellular vesicles across the blood-brain barrier: brain pharmacokinetics and effects of inflammation, Int. J. Mol. Sci., 21, 10.3390/ijms21124407 Busatto, 2021, The role of extracellular vesicles in the physiological and pathological regulation of the blood-brain barrier, FASEB Bioadv., 3, 665, 10.1096/fba.2021-00045 Zhou, 2022, Targeted drug delivery to the central nervous system using extracellular vesicles, Pharmaceuticals (Basel), 15, 10.3390/ph15030358 Monteiro-Reis, 2021, Secreted extracellular vesicle molecular cargo as a novel liquid biopsy diagnostics of central nervous system diseases, Int. J. Mol. Sci., 22, 10.3390/ijms22063267 de Jong, 2020, A CRISPR-Cas9-based reporter system for single-cell detection of extracellular vesicle-mediated functional transfer of RNA, Nat. Commun., 11, 1113, 10.1038/s41467-020-14977-8 Morel, 2013, Neuronal exosomal miRNA-dependent translational regulation of astroglial glutamate transporter GLT1, J. Biol. Chem., 288, 7105, 10.1074/jbc.M112.410944 Upadhya, 2020, Astrocyte-derived extracellular vesicles: Neuroreparative properties and role in the pathogenesis of neurodegenerative disorders, J. Control. Release, 323, 225, 10.1016/j.jconrel.2020.04.017 Potolicchio, 2005, Proteomic analysis of microglia-derived exosomes: metabolic role of the aminopeptidase CD13 in neuropeptide catabolism, J. Immunol., 175, 2237, 10.4049/jimmunol.175.4.2237 Kramer-Albers, 2020, Extracellular vesicles in the oligodendrocyte microenvironment, Neurosci. Lett., 725, 10.1016/j.neulet.2020.134915 Mathiesen, 2021, Endothelial extracellular vesicles: from keepers of health to messengers of disease, Int. J. Mol. Sci., 22, 10.3390/ijms22094640 Bahram Sangani, 2021, The role of extracellular vesicles during CNS development, Prog. Neurobiol., 205, 10.1016/j.pneurobio.2021.102124 Jin, 2021, Recent advances on extracellular vesicles in central nervous system diseases, Clin. Interv. Aging, 16, 257, 10.2147/CIA.S288415 Mahjoum, 2021, Living proof of activity of extracellular vesicles in the central nervous system, Int. J. Mol. Sci., 22, 10.3390/ijms22147294 Balaj, 2011, Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences, Nat. Commun., 2, 180, 10.1038/ncomms1180 Donoso-Quezada, 2020, State-of-the-art exosome loading and functionalization techniques for enhanced therapeutics: a review, Crit. Rev. Biotechnol., 40, 804, 10.1080/07388551.2020.1785385 Valadi, 2007, Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells, Nat. Cell Biol., 9, 654, 10.1038/ncb1596 Esmaeili, 2022, Engineering strategies for customizing extracellular vesicle uptake in a therapeutic context, Stem Cell Res Ther, 13, 129, 10.1186/s13287-022-02806-2 Heath, 2019, Endosomal escape enhancing compounds facilitate functional delivery of extracellular vesicle cargo, Nanomedicine (London), 14, 2799, 10.2217/nnm-2019-0061 Koh, 2017, Exosome-SIRPalpha, a CD47 blockade increases cancer cell phagocytosis, Biomaterials, 121, 121, 10.1016/j.biomaterials.2017.01.004 Tietjen, 2014, Molecular mechanism for differential recognition of membrane phosphatidylserine by the immune regulatory receptor Tim4, Proc. Natl. Acad. Sci. U. S. A., 111, E1463, 10.1073/pnas.1320174111 Buzas, 2018, Molecular interactions at the surface of extracellular vesicles, Semin. Immunopathol., 40, 453, 10.1007/s00281-018-0682-0 Al-Nedawi, 2009, Microvesicles: messengers and mediators of tumor progression, Cell Cycle, 8, 2014, 10.4161/cc.8.13.8988 Pauwels, 2021, Special delEVery: extracellular vesicles as promising delivery platform to the brain, Biomedicines, 9, no. 11 Gassama, 2021, Emerging roles of extracellular vesicles in the central nervous system: physiology, pathology, and therapeutic perspectives, Front. Cell. Neurosci., 15, 10.3389/fncel.2021.626043 Gratpain, 2021, Extracellular vesicles for the treatment of central nervous system diseases, Adv. Drug Deliv. Rev., 174, 535, 10.1016/j.addr.2021.05.006 Joshi, 2020, Endocytosis of extracellular vesicles and release of their cargo from endosomes, ACS Nano, 14, 4444, 10.1021/acsnano.9b10033 Rodriguez, 2022, Extracellular vesicle-based hybrid Systems for Advanced Drug Delivery, Pharmaceutics, 14, 10.3390/pharmaceutics14020267 Sutaria, 2017, Achieving the promise of therapeutic extracellular vesicles: the devil is in details of therapeutic loading, Pharm. Res., 34, 1053, 10.1007/s11095-017-2123-5 Rankin-Turner, 2021, A call for the standardised reporting of factors affecting the exogenous loading of extracellular vesicles with therapeutic cargos, Adv. Drug Deliv. Rev., 173, 479, 10.1016/j.addr.2021.04.012 Liu, 2022, Nucleic acid functionalized extracellular vesicles as promising therapeutic systems for nanomedicine, Extracell. Vesicl. Circulat. Nucleic Acids, 10.20517/evcna.2021.21 Pitt, 2016, Extracellular vesicles: masters of intercellular communication and potential clinical interventions, J. Clin. Invest., 126, 1139, 10.1172/JCI87316 Sousa, 2017, Targeting dendritic cells for the treatment of autoimmune disorders, Colloids Surf. B: Biointerfaces, 158, 237, 10.1016/j.colsurfb.2017.06.050 Choo, 2018, M1 macrophage-derived Nanovesicles potentiate the anticancer efficacy of immune checkpoint inhibitors, ACS Nano, 12, 8977, 10.1021/acsnano.8b02446 Radosinska, 2017, Therapeutic potential of hematopoietic stem cell-derived exosomes in cardiovascular disease, Adv. Exp. Med. Biol., 998, 221, 10.1007/978-981-10-4397-0_15 Xiao, 2017, Endothelial cell-derived exosomes protect SH-SY5Y nerve cells against ischemia/reperfusion injury, Int. J. Mol. Med., 40, 1201, 10.3892/ijmm.2017.3106 Phinney, 2017, Concise review: MSC-derived exosomes for cell-free therapy, Stem Cells, 35, 851, 10.1002/stem.2575 Kuo, 2017, Red blood cells: a source of extracellular vesicles, Methods Mol. Biol., 1660, 15, 10.1007/978-1-4939-7253-1_2 Fortunato, 2022, Selective isolation of extracellular vesicles from minimally processed human plasma as a translational strategy for liquid biopsies, Biomark Res., 10, 57, 10.1186/s40364-022-00404-1 Boilard, 2022, Platelet extracellular vesicles and the secretory interactome join forces in health and disease, Immunol. Rev., 312, 28, 10.1111/imr.13119 Serpe, 2021, Microglia-derived small extracellular vesicles reduce glioma growth by modifying tumor cell metabolism and enhancing glutamate clearance through miR-124, Cells, 10, 10.3390/cells10082066 Nguyen, 2022, Brain tissue-derived extracellular vesicle mediated therapy in the neonatal ischemic brain, Int. J. Mol. Sci., 23, 10.3390/ijms23020620 Yom-Tov, 2022, Extracellular vesicles over adeno-associated viruses: advantages and limitations as drug delivery platforms in precision medicine, Adv. Drug Deliv. Rev., 190, 10.1016/j.addr.2022.114535 Lai, 2012, Role of exosomes/microvesicles in the nervous system and use in emerging therapies, Front. Physiol., 3, 228, 10.3389/fphys.2012.00228 Dang, 2020, Extracellular vesicles as an efficient and versatile system for drug delivery, Cells, 9, 10.3390/cells9102191 Rufino-Ramos, 2022, Using genetically modified extracellular vesicles as a non-invasive strategy to evaluate brain-specific cargo, Biomaterials, 281, 10.1016/j.biomaterials.2022.121366 Alvarez-Erviti, 2011, Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes, Nat. Biotechnol., 29, 341, 10.1038/nbt.1807 Pham, 2021, Covalent conjugation of extracellular vesicles with peptides and nanobodies for targeted therapeutic delivery, J. Extracell. Vesicles, 10, 10.1002/jev2.12057 Mai, 2022, alphavbeta3-targeted sEVs for efficient intracellular delivery of proteins using MFG-E8, BMC Biotechnol., 22, 15, 10.1186/s12896-022-00745-7 Tian, 2018, Surface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy, Biomaterials, 150, 137, 10.1016/j.biomaterials.2017.10.012 Dar, 2021, GAPDH controls extracellular vesicle biogenesis and enhances the therapeutic potential of EV mediated siRNA delivery to the brain, Nat. Commun., 12, 6666, 10.1038/s41467-021-27056-3 Armstrong, 2017, Re-engineering extracellular vesicles as smart nanoscale therapeutics, ACS Nano, 11, 69, 10.1021/acsnano.6b07607 de Abreu, 2020, Native and bioengineered extracellular vesicles for cardiovascular therapeutics, Nat. Rev. Cardiol., 17, 685, 10.1038/s41569-020-0389-5 Richter, 2021, Approaches to surface engineering of extracellular vesicles, Adv. Drug Deliv. Rev., 173, 416, 10.1016/j.addr.2021.03.020 Lino, 2021, Engineered extracellular vesicles as brain therapeutics, J. Control. Release, 338, 472, 10.1016/j.jconrel.2021.08.037 Lai, 2015, Visualization and tracking of tumour extracellular vesicle delivery and RNA translation using multiplexed reporters, Nat. Commun., 6, 7029, 10.1038/ncomms8029 Abels, 2019, Glioblastoma-associated microglia reprogramming is mediated by functional transfer of extracellular miR-21, Cell Rep., 28, 3105, 10.1016/j.celrep.2019.08.036 Lai, 2014, Dynamic biodistribution of extracellular vesicles in vivo using a multimodal imaging reporter, ACS Nano, 8, 483, 10.1021/nn404945r Colombarolli, 2023, Extracellular vesicle molecular profiling for diagnostic purposes: an application of phage display technology, Methods Mol. Biol., 2578, 237, 10.1007/978-1-0716-2732-7_17 Zhou, 2022, Glioblastoma extracellular vesicle-specific peptides inhibit EV-induced neuronal cytotoxicity, Int. J. Mol. Sci., 23, 10.3390/ijms23137200 Kooijmans, 2016, PEGylated and targeted extracellular vesicles display enhanced cell specificity and circulation time, J. Control. Release, 224, 77, 10.1016/j.jconrel.2016.01.009 Dos Santos Rodrigues, 2020, Efficient neuronal targeting and transfection using RVG and transferrin-conjugated liposomes, Brain Res., 1734, 10.1016/j.brainres.2020.146738 Cui, 2019, RVG-modified exosomes derived from mesenchymal stem cells rescue memory deficits by regulating inflammatory responses in a mouse model of Alzheimer’s disease, Immun. Ageing, 16, 10, 10.1186/s12979-019-0150-2 Wang, 2021, Application progress of RVG peptides to facilitate the delivery of therapeutic agents into the central nervous system, RSC Adv., 11, 8505, 10.1039/D1RA00550B Kojima, 2018, Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson's disease treatment, Nat. Commun., 9, 1305, 10.1038/s41467-018-03733-8 Sugahara, 2009, Tissue-penetrating delivery of compounds and nanoparticles into tumors, Cancer Cell, 16, 510, 10.1016/j.ccr.2009.10.013 Tian, 2014, A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy, Biomaterials, 35, 2383, 10.1016/j.biomaterials.2013.11.083 Zaborowski, 2019, Membrane-bound Gaussia luciferase as a tool to track shedding of membrane proteins from the surface of extracellular vesicles, Sci. Rep., 9, 17387, 10.1038/s41598-019-53554-y Hung, 2016, A platform for actively loading cargo RNA to elucidate limiting steps in EV-mediated delivery, J. Extracell. Vesicles, 5, 31027, 10.3402/jev.v5.31027 Takayama, 2019, Click chemistry as a tool for cell engineering and drug delivery, Molecules, 24, 10.3390/molecules24010172 Lee, 2018, Facile metabolic glycan labeling strategy for exosome tracking, Biochim. Biophys. Acta Gen. Subj., 1862, 1091, 10.1016/j.bbagen.2018.02.001 Ellert-Miklaszewska, 2020, Integrin signaling in glioma pathogenesis: from biology to therapy, Int. J. Mol. Sci., 21, 10.3390/ijms21030888 Veron, 2005, Accumulation of MFG-E8/lactadherin on exosomes from immature dendritic cells, Blood Cells Mol. Dis., 35, 81, 10.1016/j.bcmd.2005.05.001 Komuro, 2022, Design and evaluation of engineered extracellular vesicle (EV)-based targeting for EGFR-overexpressing tumor cells using Monobody display, Bioengineering (Basel), 9 Kooijmans, 2018, Recombinant phosphatidylserine-binding nanobodies for targeting of extracellular vesicles to tumor cells: a plug-and-play approach, Nanoscale, 10, 2413, 10.1039/C7NR06966A Malhotra, 2017, Mycobacterium tuberculosis Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) functions as a receptor for human Lactoferrin, Front. Cell. Infect. Microbiol., 7, 245, 10.3389/fcimb.2017.00245 Pi, 2018, Nanoparticle orientation to control RNA loading and ligand display on extracellular vesicles for cancer regression, Nat. Nanotechnol., 13, 82, 10.1038/s41565-017-0012-z Man, 2020, Engineered extracellular vesicles: tailored-made nanomaterials for medical applications, Nanomaterials (Basel), 10, 10.3390/nano10091838 Osteikoetxea, 2022, Engineered Cas9 extracellular vesicles as a novel gene editing tool, J. Extracell. Vesicles, 11, 10.1002/jev2.12225 Costa Verdera, 2017, Cellular uptake of extracellular vesicles is mediated by clathrin-independent endocytosis and macropinocytosis, J. Control. Release, 266, 100, 10.1016/j.jconrel.2017.09.019 O’Brien, 2020, RNA delivery by extracellular vesicles in mammalian cells and its applications, Nat. Rev. Mol. Cell Biol., 21, 585, 10.1038/s41580-020-0251-y Mir, 2020, Extracellular vesicles as delivery vehicles of specific cellular cargo, Cells, 9, 10.3390/cells9071601 Gidlof, 2019, Proteomic profiling of extracellular vesicles reveals additional diagnostic biomarkers for myocardial infarction compared to plasma alone, Sci. Rep., 9, 8991, 10.1038/s41598-019-45473-9 Ridder, 2014, Extracellular vesicle-mediated transfer of genetic information between the hematopoietic system and the brain in response to inflammation, PLoS Biol., 12, 10.1371/journal.pbio.1001874 Ridder, 2015, Extracellular vesicle-mediated transfer of functional RNA in the tumor microenvironment, Oncoimmunology, 4, 10.1080/2162402X.2015.1008371 Zomer, 2015, In vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior, Cell, 161, 1046, 10.1016/j.cell.2015.04.042 Sterzenbach, 2017, Engineered exosomes as vehicles for biologically active proteins, Mol. Ther., 25, 1269, 10.1016/j.ymthe.2017.03.030 Rufino-Ramos, 2023, Extracellular communication between brain cells through functional transfer of Cre mRNA, Biorxiv Ye, 2020, An engineered exosome for delivering sgRNA:Cas9 ribonucleoprotein complex and genome editing in recipient cells, Biomater. Sci., 8, 2966, 10.1039/D0BM00427H Fang, 2007, Higher-order oligomerization targets plasma membrane proteins and HIV gag to exosomes, PLoS Biol., 5, 10.1371/journal.pbio.0050158 I. A. Nikonorova et al., 2021, doi: https://doi.org/10.1101/2021.09.23.461577. Santangelo, 2016, The RNA-binding protein SYNCRIP is a component of the hepatocyte Exosomal machinery controlling MicroRNA sorting, Cell Rep., 17, 799, 10.1016/j.celrep.2016.09.031 Zietzer, 2020, The RNA-binding protein hnRNPU regulates the sorting of microRNA-30c-5p into large extracellular vesicles, J. Extracell. Vesicles, 9, 1786967, 10.1080/20013078.2020.1786967 Rybarczyk, 2023, In silico and in vitro analysis of the impact of single substitutions within EXO-motifs on Hsa-MiR-1246 intercellular transfer in breast cancer cell, J. Appl. Genet., 64, 105, 10.1007/s13353-022-00730-y O'Grady, 2022, Sorting and packaging of RNA into extracellular vesicles shape intracellular transcript levels, BMC Biol., 20, 72, 10.1186/s12915-022-01277-4 Fan, 2022, A peptide derived from the N-terminus of charged multivesicular body protein 6 (CHMP6) promotes the secretion of gene editing proteins via small extracellular vesicle production, Bioengineered, 13, 4702, 10.1080/21655979.2022.2030571 Wang, 2021, Near infrared light fluorescence imaging-guided biomimetic nanoparticles of extracellular vesicles deliver indocyanine green and paclitaxel for hyperthermia combined with chemotherapy against glioma, J. Nanobiotechnol., 19, 210, 10.1186/s12951-021-00907-3 Wang, 2018, ARMMs as a versatile platform for intracellular delivery of macromolecules, Nat. Commun., 9, 960, 10.1038/s41467-018-03390-x Mulcahy, 2014, Routes and mechanisms of extracellular vesicle uptake, J. Extracell. Vesicles, 3, 10.3402/jev.v3.24641 Schneider-Poetsch, 2010, Inhibition of eukaryotic translation elongation by cycloheximide and lactimidomycin, Nat. Chem. Biol., 6, 209, 10.1038/nchembio.304 Hung, 2015, Stabilization of exosome-targeting peptides via engineered glycosylation, J. Biol. Chem., 290, 8166, 10.1074/jbc.M114.621383 Li, 2020, Fusion protein engineered exosomes for targeted degradation of specific RNAs in lysosomes: a proof-of-concept study, J. Extracell. Vesicles, 9, 1816710, 10.1080/20013078.2020.1816710 Morandi, 2022, Extracellular vesicle fusion visualized by cryo-electron microscopy, PNAS Nexus, 1, 10.1093/pnasnexus/pgac156 O’Brien, 2022, Uptake, functionality, and re-release of extracellular vesicle-encapsulated cargo, Cell Rep., 39, 10.1016/j.celrep.2022.110651 Lonn, 2016, Enhancing endosomal escape for intracellular delivery of macromolecular biologic therapeutics, Sci. Rep., 6, 32301, 10.1038/srep32301 Banskota, 2022, Engineered virus-like particles for efficient in vivo delivery of therapeutic proteins, Cell, 185, 250, 10.1016/j.cell.2021.12.021 Segel, 2021, Mammalian retrovirus-like protein PEG10 packages its own mRNA and can be pseudotyped for mRNA delivery, Science, 373, 882, 10.1126/science.abg6155 Breyne, 2022, Exogenous loading of extracellular vesicles, virus-like particles, and lentiviral vectors with supercharged proteins, Commun. Biol., 5, 485, 10.1038/s42003-022-03440-7 Azarmi, 2020, Transcellular brain drug delivery: a review on recent advancements, Int. J. Pharm., 586, 10.1016/j.ijpharm.2020.119582 Terstappen, 2021, Strategies for delivering therapeutics across the blood-brain barrier, Nat. Rev. Drug Discov., 20, 362, 10.1038/s41573-021-00139-y Choi, 2022, Strategies for targeted delivery of exosomes to the brain: advantages and challenges, Pharmaceutics, 14, 10.3390/pharmaceutics14030672 Ramos-Zaldivar, 2022, Extracellular vesicles through the blood-brain barrier: a review, Fluids Barriers CNS, 19, 60, 10.1186/s12987-022-00359-3 Wiklander, 2015, Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting, J. Extracell. Vesicles, 4, 26316, 10.3402/jev.v4.26316 Webb, 2018, Human neural stem cell extracellular vesicles improve tissue and functional recovery in the murine thromboembolic stroke model, Transl. Stroke Res., 9, 530, 10.1007/s12975-017-0599-2 Driedonks, 2022, Pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to Macaca nemestrina, J. Extracell. Biol., 1, 10.1002/jex2.59 Nieland, 2021, Extracellular vesicle-mediated bilateral communication between glioblastoma and astrocytes, Trends Neurosci., 44, 215, 10.1016/j.tins.2020.10.014 Oushy, 2018, Glioblastoma multiforme-derived extracellular vesicles drive normal astrocytes towards a tumour-enhancing phenotype, Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci., 373, 10.1098/rstb.2016.0477 Maas, 2020, Glioblastoma hijacks microglial gene expression to support tumor growth, J. Neuroinflammation, 17, 120, 10.1186/s12974-020-01797-2 Herman, 2021, Intranasal delivery of mesenchymal stem cells-derived extracellular vesicles for the treatment of neurological diseases, Stem Cells, 39, 1589, 10.1002/stem.3456 De Carvalho, 2021, Intranasal drug delivery to overcome the blood–brain barrier, South African General Practit., 2, 220, 10.36303/SAGP.2021.2.6.0095 Losurdo, 2020, Intranasal delivery of mesenchymal stem cell-derived extracellular vesicles exerts immunomodulatory and neuroprotective effects in a 3xTg model of Alzheimer's disease, Stem Cells Transl. Med., 9, 1068, 10.1002/sctm.19-0327 Zhdanova, 2021, Effect of intranasal Administration of Multipotent Mesenchymal Stromal Cell Exosomes on memory of mice in Alzheimer’s disease model, Bull. Exp. Biol. Med., 170, 575, 10.1007/s10517-021-05109-3 Cieslik, 2022, Extracellular vesicles-Oral therapeutics of the future, Int. J. Mol. Sci., 23, 10.3390/ijms23147554 Umezu, 2021, Acerola exosome-like nanovesicles to systemically deliver nucleic acid medicine via oral administration, Mol. Ther. Meth. Clin. Dev., 21, 199, 10.1016/j.omtm.2021.03.006 Librizzi, 2022, Ultrasounds induce blood-brain barrier opening across a sonolucent polyolefin plate in an in vitro isolated brain preparation, Sci. Rep., 12, 2906, 10.1038/s41598-022-06791-7 Presset, 2022, First Metabolomic signature of blood-brain barrier opening induced by microbubble-assisted ultrasound, Front. Mol. Neurosci., 15, 10.3389/fnmol.2022.888318 Haney, 2022, Biodistribution of biomimetic drug carriers, mononuclear cells, and extracellular vesicles, in nonhuman Primates, Adv. Biol. (Weinh), 6 Liu, 2005, Functional correction of CNS phenotypes in a lysosomal storage disease model using adeno-associated virus type 4 vectors, J. Neurosci., 25, 9321, 10.1523/JNEUROSCI.2936-05.2005 Chandran, 2022, Assessment of AAV9 Distribution and Transduction in Rats after Administration through Intrastriatal, Intracisterna Magna and Lumbar Intrathecal Routes, Gene Ther. Elia, 2019, Intracerebral injection of extracellular vesicles from mesenchymal stem cells exerts reduced Abeta plaque burden in early stages of a preclinical model of Alzheimer’s disease, Cells, 8, 10.3390/cells8091059 Fricke, 2021, Proinflammatory extracellular vesicle-mediated signaling contributes to the induction of Neuroinflammation in animal models of Endotoxemia and peripheral surgical stress, Cell. Mol. Neurobiol., 41, 1325, 10.1007/s10571-020-00905-3 Baulch, 2016, Cranial grafting of stem cell-derived microvesicles improves cognition and reduces neuropathology in the irradiated brain, Proc. Natl. Acad. Sci. U. S. A., 113, 4836, 10.1073/pnas.1521668113 Ioannides, 2020, Evaluating different routes of extracellular vesicle administration for cranial therapies, J Cancer Metastasis Treat, 6 Kang, 2021, Biodistribution of extracellular vesicles following administration into animals: a systematic review, J. Extracell. Vesicles, 10, 10.1002/jev2.12085 Aly, 2015, Intranasal gene delivery for treating Parkinson’s disease: overcoming the blood-brain barrier, Expert. Opin. Drug. Deliv., 12, 1923, 10.1517/17425247.2015.1069815 Musumeci, 2019, Epilepsy disease and nose-to-brain delivery of polymeric nanoparticles: an overview, Pharmaceutics, 11, 10.3390/pharmaceutics11030118 Patras, 2022, Trojan horse treatment based on PEG-coated extracellular vesicles to deliver doxorubicin to melanoma in vitro and in vivo, Cancer Biol. Ther., 23, 1, 10.1080/15384047.2021.2003656 Jhan, 2021, Polymer-coated extracellular vesicles for selective Codelivery of chemotherapeutics and siRNA to Cancer cells, ACS Appl. Bio. Mater., 4, 1294, 10.1021/acsabm.0c01153 Feng, 2021, Reversing the surface charge of MSC-derived small extracellular vesicles by epsilonPL-PEG-DSPE for enhanced osteoarthritis treatment, J. Extracell. Vesicles, 10, 10.1002/jev2.12160 Vella, 2016, Focus on extracellular vesicles: exosomes and their role in protein trafficking and biomarker potential in Alzheimer’s and Parkinson’s disease, Int. J. Mol. Sci., 17, 173, 10.3390/ijms17020173 Liu, 2022, Extracellular vesicle PD-L1 in reshaping tumor immune microenvironment: biological function and potential therapy strategies, Cell Commun. Sig., 20, 14, 10.1186/s12964-021-00816-w Yeo, 2013, Mesenchymal stem cell: an efficient mass producer of exosomes for drug delivery, Adv. Drug Deliv. Rev., 65, 336, 10.1016/j.addr.2012.07.001 Zhou, 2021, Challenges and advances in clinical applications of mesenchymal stromal cells, J. Hematol. Oncol., 14, 24, 10.1186/s13045-021-01037-x Qian, 2022, Mesenchymal stem cell-derived extracellular vesicles alleviate M1 microglial activation in brain injury of mice with subarachnoid hemorrhage via microRNA-140-5p delivery, Int. J. Neuropsychopharmacol., 25, 328, 10.1093/ijnp/pyab096 Van Hoecke, 2021, Anti-inflammatory mesenchymal stromal cell-derived extracellular vesicles improve pathology in Niemann-pick type C disease, Biomedicines, 9, 10.3390/biomedicines9121864 Didiot, 2016, Exosome-mediated delivery of Hydrophobically modified siRNA for huntingtin mRNA silencing, Mol. Ther., 24, 1836, 10.1038/mt.2016.126 Haney, 2015, Exosomes as drug delivery vehicles for Parkinson’s disease therapy, J. Control. Release, 207, 18, 10.1016/j.jconrel.2015.03.033 Haney, 2019, TPP1 delivery to lysosomes with extracellular vesicles and their enhanced brain distribution in the animal model of batten disease, Adv. Healthc. Mater., 8, 10.1002/adhm.201801271 Yu, 2022, Extracellular vesicle-mediated delivery of circDYM alleviates CUS-induced depressive-like behaviours, J. Extracell. Vesicles, 11, 10.1002/jev2.12185 Tian, 2021, Targeted delivery of neural progenitor cell-derived extracellular vesicles for anti-inflammation after cerebral ischemia, Theranostics, 11, 6507, 10.7150/thno.56367 Meyer, 2017, Pseudotyping exosomes for enhanced protein delivery in mammalian cells, Int. J. Nanomedicine, 12, 3153, 10.2147/IJN.S133430 Tian, 2022, Immune checkpoint inhibition in GBM primed with radiation by engineered extracellular vesicles, ACS Nano, 16, 1940, 10.1021/acsnano.1c05505 Jia, 2018, NRP-1 targeted and cargo-loaded exosomes facilitate simultaneous imaging and therapy of glioma in vitro and in vivo, Biomaterials, 178, 302, 10.1016/j.biomaterials.2018.06.029 Ye, 2018, Methotrexate-loaded extracellular vesicles functionalized with therapeutic and targeted peptides for the treatment of glioblastoma Multiforme, ACS Appl. Mater. Interfaces, 10, 12341, 10.1021/acsami.7b18135 Adamus, 2022, Glioma-targeted delivery of exosome-encapsulated antisense oligonucleotides using neural stem cells, Mol. Ther. Nucleic Acids, 27, 611, 10.1016/j.omtn.2021.12.029 Do, 2019, Targeted delivery of lysosomal enzymes to the endocytic compartment in human cells using engineered extracellular vesicles, Sci. Rep., 9, 17274, 10.1038/s41598-019-53844-5 Heiland, 2017, Comprehensive analysis of PD-L1 expression in glioblastoma multiforme, Oncotarget, 8, 42214, 10.18632/oncotarget.15031 Phan, 2020, Unleashing the therapeutic potential of apoptotic bodies, Biochem. Soc. Trans., 48, 2079, 10.1042/BST20200225 Boohaker, 2012, The use of therapeutic peptides to target and to kill cancer cells, Curr. Med. Chem., 19, 3794, 10.2174/092986712801661004 Wang, 2021, A microfluidics-based scalable approach to generate extracellular vesicles with enhanced therapeutic microRNA loading for intranasal delivery to mouse glioblastomas, ACS Nano, 15, 18327, 10.1021/acsnano.1c07587 Brossa, 2021, Coincubation as miR-loading strategy to improve the anti-tumor effect of stem cell-derived EVs, Pharmaceutics, 13, 10.3390/pharmaceutics13010076 Giebel, 2017, Clinical potential of mesenchymal stem/stromal cell-derived extracellular vesicles, Stem Cell Investig., 4, 84, 10.21037/sci.2017.09.06 Bang, 2022, Stem cell-derived extracellular vesicle therapy for acute brain insults and neurodegenerative diseases, BMB Rep., 55, 20, 10.5483/BMBRep.2022.55.1.162 Choi, 2022, Therapeutic exosomes for various human diseases: special issue of BMB reports in 2022, BMB Rep., 55, 1, 10.5483/BMBRep.2022.55.1.011 Lamnabhi-Lagarrigu, 2013 Hsu, 2003, Exosomes as a tumor vaccine: enhancing potency through direct loading of antigenic peptides, J. Immunother., 26, 440, 10.1097/00002371-200309000-00007 Escudier, 2005, Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial, J. Transl. Med., 3, 10, 10.1186/1479-5876-3-10 Morse, 2005, A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer, J. Transl. Med., 3, 9, 10.1186/1479-5876-3-9 Guo, 2019, Autologous tumor cell–derived microparticle-based targeted chemotherapy in lung cancer patients with malignant pleural effusion, Sci. Transl. Med., 11, 10.1126/scitranslmed.aat5690 Warnecke, 2021, First-in-human intracochlear application of human stromal cell-derived extracellular vesicles, J. Extracell. Vesicles, 10, 10.1002/jev2.12094 Warnecke, 2020, Extracellular vesicles from human multipotent stromal cells protect against hearing loss after noise trauma in vivo, Clin. Transl. Med., 10, 10.1002/ctm2.262 Ciferri, 2021, Extracellular vesicles as biomarkers and therapeutic tools: from pre-clinical to clinical applications, Biology (Basel), 10 Zachariah, 2018, Blood-based biomarkers for the diagnosis and monitoring of gliomas, Neuro-Oncology, 20, 1155, 10.1093/neuonc/noy074 Kumar, 2020, Challenges in biomaterial-based drug delivery approach for the treatment of neurodegenerative diseases: opportunities for extracellular vesicles, Int. J. Mol. Sci., 22, no. 1