Cell-derived nanovesicle-mediated drug delivery to the brain: Principles and strategies for vesicle engineering
Open accessAbstract
Developing strategies toward safe and effective drug delivery into the central nervous system (CNS) with improved targeting abilities and reduced off-target effects is crucial. CNS-targeted drug carriers made of synthetic molecules raise concerns about their biodegradation, clearance, immune responses, and neurotoxicity. Cell-derived nanovesicles (CDNs) have recently been applied in CNS-targeted drug delivery, because of their intrinsic stability, biocompatibility, inherent homing capability, and the ability to penetrate through biological barriers, including the blood-brain barrier. Among these CDNs, extracellular vesicles and exosomes are the most studied because their surface can be engineered and modified to cater to brain targeting. In this review, we focus on the application of CDNs in brain-targeted drug delivery to treat neurological diseases. We cover recently developed methods of exosome derivation and engineering, including exosome-like particles, hybrid exosomes, exosome-associated adeno-associated viruses, and envelope protein nanocages. Finally, we discuss the limitations and project the future development of the CDN-based brain-targeted delivery systems, and conclude that engineered CDNs hold great potential in the treatment of neurological diseases.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Engineered exosomes carrying RVG-Lamp2b can efficiently cross the blood-brain barrier and deliver catalase mRNA, resulting in a reduction of 6-OHDA-mediated neuroinflammation in a mouse model of Parkinson's disease.
“The designed exosome carrying RVG-Lamp2b was able to efficiently cross the blood–brain barrier (BBB) and deliver the catalase mRNA, resulting in a reduction of 6-OHDA-mediated neuroinflammation in a mouse model of Parkinson’s disease [101, 103].”
From Exosome for mRNA delivery: Strategies and therapeutic applications (2024) · cites this paper as [103]
Two main approaches can be used to enhance targeting ability of exosomes: direct chemical modification or indirect genetic engineering.
“Two main approaches can be used to enhance the targeting ability of exosomes for specific applications: direct modification of exosomes by chemical means or, indirect manipulation of the donor cells through genetic engineering techniques [89, 103, 118–120]”
From Exosome for mRNA delivery: Strategies and therapeutic applications (2024) · cites this paper as [103]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Astrocyte-endothelial interactions at the blood-brain barrier
Abbott, N. J., Rönnbäck, L., & Hansson, E. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1824 · Cited by 5,595 · see citing works
Tumour exosome integrins determine organotropic metastasis
Hoshino, A., Costa-Silva, B., Shen, T.-L., Rodrigues, G., Hashimoto, A., Tesic Mark, M., Molina, H., Kohsaka, S., Di Giannatale, A., Ceder, S., et al. (2015) · Nature · doi:10.1038/nature15756 · Cited by 5,101 · see citing works
Self-citationDelivery of siRNA to the mouse brain by systemic injection of targeted exosomes
Alvarez-Erviti, L., Seow, Y., Yin, H., Betts, C., Lakhal, S., & Wood, M. J. A. (2011) · Nature Biotechnology · doi:10.1038/nbt.1807 · Cited by 4,930 · see citing works
Daneman, R., & Prat, A. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a020412 · Cited by 3,437 · see citing works
Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders
Sweeney, M. D., Sagare, A. P., & Zlokovic, B. V. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.188 · Cited by 3,076 · see citing works
Current knowledge on exosome biogenesis and release
Hessvik, N. P., & Llorente, A. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2595-9 · Cited by 2,362 · see citing works
Exosomes as drug delivery vehicles for Parkinson’s disease therapy
Haney, M. J., Klyachko, N. L., Zhao, Y., Gupta, R., Plotnikova, E. G., He, Z., Patel, T., Piroyan, A., Sokolsky, M., Kabanov, A. V., et al. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.03.033 · Cited by 2,009 · see citing works
Drug Transport across the Blood–Brain Barrier
Pardridge, W. M. (2012) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2012.126 · Cited by 1,994 · see citing works
A blood–brain barrier overview on structure, function, impairment, and biomarkers of integrity
Kadry, H., Noorani, B., & Cucullo, L. (2020) · Fluids and Barriers of the CNS · doi:10.1186/s12987-020-00230-3 · Cited by 1,853 · see citing works
Tian, Y., Li, S., Song, J., Ji, T., Zhu, M., Anderson, G. J., Wei, J., & Nie, G. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.11.083 · Cited by 1,809 · see citing works
Wiklander, O. P. B., Nordin, J. Z., O'Loughlin, A., Gustafsson, Y., Corso, G., Mäger, I., Vader, P., Lee, Y., Sork, H., Seow, Y., et al. (2015) · Journal of Extracellular Vesicles · doi:10.3402/jev.v4.26316 · Cited by 1,730 · see citing works
Engineering exosomes for targeted drug delivery
Liang, Y., Duan, L., Lu, J., & Xia, J. (2021) · Theranostics · doi:10.7150/thno.52570 · Cited by 1,547 · see citing works
Self-citationDevelopment of exosome-encapsulated paclitaxel to overcome MDR in cancer cells
Kim, M. S., Haney, M. J., Zhao, Y., Mahajan, V., Le‐Deygen, I. M., Klyachko, N. L., Inskoe, E., Piroyan, A., Sokolsky‐Papkov, M., Okolie, O., et al. (2015) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2015.10.012 · Cited by 1,498 · see citing works
Akers, J. C., Gonda, D., Kim, R., Carter, B. S., & Chen, C. C. (2013) · Journal of Neuro-Oncology · doi:10.1007/s11060-013-1084-8 · Cited by 1,423 · cited 2× · see citing works
“31 – 33 Exosomes interact with the target cells through different mechanisms.”
Zhuang, X., Xiang, X., Grizzle, W., Sun, D., Zhang, S., Axtell, R. C., Ju, S., Mu, J., Zhang, L., Steinman, L., et al. (2011) · Molecular Therapy · doi:10.1038/mt.2011.164 · Cited by 1,356 · see citing works
Self-citationSurface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy
Tian, T., Zhang, H.-X., He, C.-P., Fan, S., Zhu, Y.-L., Qi, C., Huang, N.-P., Xiao, Z.-D., Lu, Z.-H., Tannous, B. A., et al. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2017.10.012 · Cited by 1,154 · see citing works
Self-citationXin, H., Li, Y., Cui, Y., Yang, J. J., Zhang, Z. G., & Chopp, M. (2013) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2013.152 · Cited by 985 · see citing works
Yang, T., Martin, P. B., Fogarty, B., Brown, A. H., Schurman, K., Phipps, R. J., Yin, V. P., Lockman, P. R., & Bai, S. (2015) · Pharmaceutical Research · doi:10.1007/s11095-014-1593-y · Cited by 980 · see citing works
Xin, H., Li, Y., Buller, B., Katakowski, M., Zhang, Y., Wang, X., Shang, X., Zhang, Z. G., & Chopp, M. (2012) · Stem Cells · doi:10.1002/stem.1129 · Cited by 897 · see citing works
Generation and testing of clinical-grade exosomes for pancreatic cancer
Mendt, M. C., Kamerkar, S., Sugimoto, H., McAndrews, K. M., Wu, C.-C., Gagea, M., Yang, S., Blanko, E. V. R., Peng, Q., Ma, X., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.99263 · Cited by 795 · see citing works
The blood–brain and the blood–cerebrospinal fluid barriers: function and dysfunction
Engelhardt, B., & Sorokin, L. M. (2009) · Seminars in Immunopathology · doi:10.1007/s00281-009-0177-0 · Cited by 792 · see citing works
Doeppner, T. R., Herz, J., Görgens, A., Schlechter, J., Ludwig, A., Radtke, S., de Miroschedji, K., Horn, P. A., Giebel, B., & Hermann, D. M. (2015) · Stem Cells Translational Medicine · doi:10.5966/sctm.2015-0078 · Cited by 773 · see citing works
Jia, G., Han, Y., An, Y., Ding, Y., He, C., Wang, X., & Tang, Q. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.06.029 · Cited by 753 · see citing works
Kojima, R., Bojar, D., Rizzi, G., Hamri, G. C.-E., El-Baba, M. D., Saxena, P., Ausländer, S., Tan, K. R., & Fussenegger, M. (2018) · Nature Communications · doi:10.1038/s41467-018-03733-8 · Cited by 748 · see citing works
Zhang, Y., Chopp, M., Meng, Y., Katakowski, M., Xin, H., Mahmood, A., & Xiong, Y. (2015) · Journal of neurosurgery · doi:10.3171/2014.11.jns14770 · Cited by 737 · see citing works
Xin, H., Li, Y., Liu, Z., Wang, X., Shang, X., Cui, Y., Zhang, Z. G., & Chopp, M. (2013) · Stem Cells · doi:10.1002/stem.1409 · Cited by 724 · see citing works
Characteristics of Compounds that Cross the Blood-Brain Barrier
Banks, W. A. (2009) · BMC Neurology · doi:10.1186/1471-2377-9-s1-s3 · Cited by 710 · see citing works
Plasma exosomal α-synuclein is likely CNS-derived and increased in Parkinson’s disease
Shi, M., Liu, C., Cook, T. J., Bullock, K. M., Zhao, Y., Ginghina, C., Li, Y., Aro, P., Dator, R., He, C., et al. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1314-y · Cited by 676 · see citing works
Exosome–Liposome Hybrid Nanoparticles Deliver CRISPR/Cas9 System in MSCs
Lin, Y., Wu, J., Gu, W., Huang, Y., Tong, Z., Huang, L., & Tan, J. (2018) · Advanced Science · doi:10.1002/advs.201700611 · Cited by 625 · see citing works
Macrophage exosomes as natural nanocarriers for protein delivery to inflamed brain
Yuan, D., Zhao, Y., Banks, W. A., Bullock, K. M., Haney, M., Batrakova, E., & Kabanov, A. V. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.07.011 · Cited by 607 · see citing works
Exosome Mediated Delivery of miR-124 Promotes Neurogenesis after Ischemia
Yang, J., Zhang, X., Chen, X., Wang, L., & Yang, G. (2017) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2017.04.010 · Cited by 592 · see citing works
Self-citationYim, N., Ryu, S.-W., Choi, K., Lee, K. R., Lee, S., Choi, H., Kim, J., Shaker, M. R., Sun, W., Park, J.-H., et al. (2016) · Nature Communications · doi:10.1038/ncomms12277 · Cited by 578 · see citing works
Haraszti, R. A., Miller, R., Stoppato, M., Sere, Y. Y., Coles, A., Didiot, M.-C., Wollacott, R., Sapp, E., Dubuke, M. L., Li, X., et al. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2018.09.015 · Cited by 567 · see citing works
Tumor-Derived Extracellular Vesicles Breach the Intact Blood–Brain Barrier via Transcytosis
Morad, G., Carman, C. V., Hagedorn, E. J., Perlin, J. R., Zon, L. I., Mustafaoğlu, N., Park, T., Ingber, D. E., Daisy, C. C., & Moses, M. A. (2019) · ACS Nano · doi:10.1021/acsnano.9b04397 · Cited by 561 · see citing works
Banks, W. A., Sharma, P., Bullock, K. M., Hansen, K. M., Ludwig, N., & Whiteside, T. L. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124407 · Cited by 561 · cited 1× · see citing works
“29 Thus, deciphering the mechanism of this highly selective barrier will further facilitate the development of new approaches to aid the crossing of the BBB by rationally designing effective exo-some-based brain delivery systems.”
Dopamine-loaded blood exosomes targeted to brain for better treatment of Parkinson’s disease
Qu, M., Lin, Q., Huang, L., Fu, Y., Wang, L., He, S., Fu, Y., Yang, S., Zhang, Z., Zhang, L., et al. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2018.08.035 · Cited by 543 · see citing works
Elucidation of Exosome Migration Across the Blood–Brain Barrier Model In Vitro
Chen, C. C., Liu, L., Ma, F., Wong, C. W., Guo, X. E., Chacko, J. V., Farhoodi, H. P., Zhang, S. X., Zimak, J., Ségaliny, A., et al. (2016) · Cellular and Molecular Bioengineering · doi:10.1007/s12195-016-0458-3 · Cited by 537 · see citing works
Piffoux, M., Silva, A., Wilhelm, C., Gazeau, F., & Tareste, D. C. (2018) · ACS Nano · doi:10.1021/acsnano.8b02053 · Cited by 463 · see citing works
Exosome engineering: Current progress in cargo loading and targeted delivery
Fu, S., Wang, Y., Xia, X., & Zheng, J. C. (2020) · NanoImpact · doi:10.1016/j.impact.2020.100261 · Cited by 444 · see citing works
Anchor peptide captures, targets, and loads exosomes of diverse origins for diagnostics and therapy
Gao, X., Ran, N., Dong, X., Zuo, B., Yang, R., Zhou, Q., Moulton, H. M., Seow, Y., & Yin, H. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aat0195 · Cited by 426 · see citing works
Monocarboxylate transporters in the brain and in cancer
Pérez‐Escuredo, J., Hée, V. F. V., Sboarina, M., Falces, J., Payen, V. L., Pellerin, L., & Sonveaux, P. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2016.03.013 · Cited by 407 · see citing works
In Vivo Neuroimaging of Exosomes Using Gold Nanoparticles
Betzer, O., Perets, N., Angel, A., Motiei, M., Sadan, T., Yadid, G., Offen, D., & Popovtzer, R. (2017) · ACS Nano · doi:10.1021/acsnano.7b04495 · Cited by 404 · see citing works
Exosomal cargo-loading and synthetic exosome-mimics as potential therapeutic tools
Li, S.-P., Lin, Z., Jiang, X., & Yu, X. (2018) · Acta Pharmacologica Sinica · doi:10.1038/aps.2017.178 · Cited by 395 · see citing works
Liang, Y., Xu, X., Li, X., Xiong, J., Li, B., Duan, L., Wang, D., & Xia, J. (2020) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.0c10458 · Cited by 391 · see citing works
Self-citationEfficient production and enhanced tumor delivery of engineered extracellular vesicles
Watson, D. C., Bayik, D., Srivatsan, A., Bergamaschi, C., Valentin, A., Niu, G., Bear, J., Monninger, M., Sun, M., Morales-Kastresana, A., et al. (2016) · Biomaterials · doi:10.1016/j.biomaterials.2016.07.003 · Cited by 385 · see citing works
Self-citationBernardo-Castro, S., Sousa, J. A., Brás, A., Cecília, C., Rodrigues, B., Almendra, L., Machado, C., Santo, G., da Silva, F. A. D. A., Ferreira, L., et al. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.594672 · Cited by 383 · see citing works
Yang, L., Han, B., Zhang, Z., Wang, S., Bai, Y., Zhang, Y., Tang, Y., Du, L., Xu, L., Wu, F., et al. (2020) · Circulation · doi:10.1161/circulationaha.120.045765 · Cited by 376 · see citing works
Self-citationXian, P., Hei, Y., Wang, R., Wang, T., Yang, J., Li, J., Di, Z., Liu, Z., Baskys, A., Liu, W., et al. (2019) · Theranostics · doi:10.7150/thno.33872 · Cited by 375 · see citing works
Engineered Exosomes as Vehicles for Biologically Active Proteins
Sterzenbach, U., Putz, U., Low, L., Silke, J., Tan, S., & Howitt, J. A. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.03.030 · Cited by 341 · see citing works
Kim, H. Y., Kim, T. J., Kang, L., Kim, Y. J., Kang, M. K., Kim, J., Ryu, J. H., Hyeon, T., Yoon, B., Ko, S., et al. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2020.119942 · Cited by 322 · see citing works
Chen, H.-X., Liang, F.-C., Gu, P., Xu, B.-L., Xu, H.-J., Wang, W.-T., Hou, J.-Y., Xie, D.-X., Chai, X.-Q., & An, S.-J. (2020) · Cell Death & Disease · doi:10.1038/s41419-020-2473-5 · Cited by 319 · see citing works
Li, Z., Zhou, X., Wei, M., Gao, X., Zhao, L., Shi, R., Sun, W., Duan, Y., Yang, G., & Yuan, L. (2019) · Nano Letters · doi:10.1021/acs.nanolett.8b02689 · Cited by 318 · see citing works
Kim, G., Kim, M., Lee, Y., Byun, J. W., Hwang, D. W., & Lee, M. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.11.009 · Cited by 313 · see citing works
Cheng, L., Zhang, X., Tang, J., Lv, Q., & Liu, J. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2021.120964 · Cited by 307 · see citing works
Cui, G.-H., Guo, H.-D., Li, H., Zhai, Y., Gong, Z.-B., Wu, J., Liu, J.-S., Dong, Y.-R., Hou, S.-X., & Liu, J.-R. (2019) · Immunity & Ageing · doi:10.1186/s12979-019-0150-2 · Cited by 305 · see citing works
Matsumoto, J., Stewart, T., Sheng, L., Li, N., Bullock, K. M., Song, N., Shi, M. Y., Banks, W. A., & Zhang, J. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0470-4 · Cited by 294 · see citing works
Webb, R. L., Kaiser, E. E., Scoville, S. L., Thompson, T. A., Fatima, S., Pandya, C., Sriram, K., Swetenburg, R. L., Vaibhav, K., Arbab, A. S., et al. (2017) · Translational Stroke Research · doi:10.1007/s12975-017-0599-2 · Cited by 284 · see citing works
Exosome-mediated targeted delivery of miR-210 for angiogenic therapy after cerebral ischemia in mice
Zhang, H., Wu, J. S., Wu, J., Fan, Q. W., Zhou, J., Wu, J., Liu, S., Zang, J., Ye, J., Xiao, M., et al. (2019) · Journal of Nanobiotechnology · doi:10.1186/s12951-019-0461-7 · Cited by 281 · see citing works
Self-citationTargeted exosome-mediated delivery of opioid receptor Mu siRNA for the treatment of morphine relapse
Liu, Y., Li, D., Liu, Z., Zhou, Y., Chu, D., Li, X., Jiang, X., Hou, D., Chen, X., Chen, Y., et al. (2015) · Scientific Reports · doi:10.1038/srep17543 · Cited by 280 · see citing works
Self-citationReceptor mediated uptake of peptides that bind the human transferrin receptor
Lee, J. H., Engler, J. A., Collawn, J. F., & Moore, B. A. (2001) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2001.02073.x · Cited by 280 · see citing works
Ding, M., Shen, Y., Wang, P., Xie, Z., Xu, S., Zhu, Z., Wang, Y., Lyu, Y., Dewei, W., Xu, L., et al. (2018) · Neurochemical Research · doi:10.1007/s11064-018-2641-5 · Cited by 279 · see citing works
Current Knowledge on Exosome Biogenesis, Cargo-Sorting Mechanism and Therapeutic Implications
Xie, S., Zhang, Q., & Jiang, L. (2022) · Membranes · doi:10.3390/membranes12050498 · Cited by 262 · see citing works
A platform for actively loading cargo RNA to elucidate limiting steps in EV‐mediated delivery
Hung, M. E., & Leonard, J. N. (2016) · Journal of Extracellular Vesicles · doi:10.3402/jev.v5.31027 · Cited by 251 · see citing works
Tian, T., Cao, L., He, C. H., Ye, Q., Liang, R., You, W., Zhang, H., Wu, J., Ye, J., Tannous, B. A., et al. (2021) · Theranostics · doi:10.7150/thno.56367 · Cited by 242 · see citing works
Self-citationExosome-mediated delivery of gene vectors for gene therapy
Duan, L., Xu, L., Xu, X., Qin, Z., Zhou, X., Xiao, Y., Liang, Y., & Xia, J. (2021) · Nanoscale · doi:10.1039/d0nr07622h · Cited by 238 · see citing works
Self-citationLi, L., He, D., Guo, Q., Zhang, Z., Ru, D., Wang, L., Gong, K., Liu, F., Duan, Y., & He, L. N. (2022) · Journal of Nanobiotechnology · doi:10.1186/s12951-022-01264-5 · Cited by 232 · see citing works
Role of Exosomes in Central Nervous System Diseases
Liu, W., Bai, X., Zhang, A., Huang, J., Xu, S., & Zhang, J. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00240 · Cited by 222 · see citing works
Active endocannabinoids are secreted on extracellular membrane vesicles
Gabrielli, M., Battista, N., Riganti, L., Prada, I., Antonucci, F., Cantone, L., Matteoli, M., Maccarrone, M., & Verderio, C. (2015) · The EMBO Reports · doi:10.15252/embr.201439668 · Cited by 221 · see citing works
Functional siRNA Delivery by Extracellular Vesicle–Liposome Hybrid Nanoparticles
Evers, M. J. W., van de Wakker, S. I., de Groot, E. M., de Jong, O. G., Gitz-Francois, J. J., Seinen, C. W., Sluijter, J. P. G., Schiffelers, R. M., & Vader, P. (2021) · Advanced Healthcare Materials · doi:10.1002/adhm.202101202 · Cited by 221 · see citing works
Overview and Update on Methods for Cargo Loading into Extracellular Vesicles
Han, Y., Jones, T. W., Dutta, S., Zhu, Y., Wang, X., Narayanan, S. P., Fagan, S. C., & Zhang, D. (2021) · Processes · doi:10.3390/pr9020356 · Cited by 213 · see citing works
Maletı́nská, L., Blakely, E. A., Bjornstad, K. A., Deen, D. F., Knoff, L. J., & Forte, T. M. (2000) · PubMed · Cited by 205 · see citing works
Mesenchymal stem cell-derived exosome: a promising alternative in the therapy of Alzheimer’s disease
Guo, M., Yin, Z., Chen, F., & Lei, P. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00670-x · Cited by 203 · see citing works
Neurodegenerative disease: Brain windfall
Gammon, K. (2014) · Nature · doi:10.1038/nj7526-299a · Cited by 202 · see citing works
Lombardi, M., Parolisi, R., Scaroni, F., Bonfanti, E., Gualerzi, A., Gabrielli, M., de Rosbo, N. K., Uccelli, A., Giussani, P., Viani, P., et al. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02049-1 · Cited by 188 · see citing works
Zheng, Y., He, R., Wang, P., Shi, Y., Zhao, L., & Liang, J. (2019) · Biomaterials Science · doi:10.1039/c8bm01449c · Cited by 184 · see citing works
Vogel, A. D., Upadhya, R., & Shetty, A. K. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.11.026 · Cited by 183 · see citing works
Transcytosis of Macromolecules at the Blood–Brain Barrier
Preston, J. E., Abbott, N. J., & Begley, D. J. (2014) · Advances in pharmacology · doi:10.1016/bs.apha.2014.06.001 · Cited by 182 · see citing works
Han, L., Huang, R., Liu, S., et al. (2010) · Molecular Pharmaceutics · doi:10.1021/mp100185f · Cited by 182 · see citing works
Exosomal delivery of therapeutic modulators through the blood–brain barrier; promise and pitfalls
Heidarzadeh, M., Özdemir, Y., Kaya, M., Abriz, A. E., Zarebkohan, A., Rahbarghazi, R., & Sokullu, E. (2021) · Cell & Bioscience · doi:10.1186/s13578-021-00650-0 · Cited by 175 · see citing works
Chen, C., Sun, M., Wang, J., Su, L., Lin, J., & Yan, X. (2021) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12163 · Cited by 166 · see citing works
Self-citationExtracellular vesicle‐mediated delivery of circDYM alleviates CUS‐induced depressive‐like behaviours
Yu, X., Bai, Y., Han, B., Ju, M., Tang, T., Shen, L., Li, M., Yang, L., Zhang, Z., Hu, G., et al. (2022) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12185 · Cited by 164 · see citing works
Yang, L., Zhai, Y., Hao, Y., Zhu, Z., & Cheng, G. (2019) · Small · doi:10.1002/smll.201906273 · Cited by 159 · see citing works
Drug Delivery Across The Blood–Brain Barrier: Recent Advances in The Use of Nanocarriers
Mulvihill, J. J., Cunnane, E. M., Ross, A. M., Duskey, J. T., Tosi, G., & Grabrucker, A. M. (2020) · Nanomedicine · doi:10.2217/nnm-2019-0367 · Cited by 159 · see citing works
Yang, J., Wu, S., Hou, L., Zhu, D., Yin, S., Yang, G., & Wang, Y. (2020) · Molecular Therapy Nucleic Acids · doi:10.1016/j.omtn.2020.06.013 · Cited by 154 · see citing works
Expression of Large Amino Acid Transporter LAT1 in Rat Brain Endothelium
Duelli, R., Enerson, B. E., Gerhart, D. Z., & Drewes, L. R. (2000) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200011000-00005 · Cited by 153 · see citing works
Yu, Z., Wen, Y., Jiang, N., Li, Z., Guan, J., Zhang, Y., Deng, C., Zhao, L., Zheng, S. G., Zhu, Y., et al. (2022) · Biomaterials · doi:10.1016/j.biomaterials.2022.121484 · Cited by 153 · see citing works
Cova, L., Armentero, M., Zennaro, E., Calzarossa, C., Bossolasco, P., Busca, G. A., Deliliers, G. L., Polli, E. E., Nappi, G., Silani, V., et al. (2009) · Brain Research · doi:10.1016/j.brainres.2009.11.041 · Cited by 152 · see citing works
Li, Y., Liu, Z., Song, Y., Pan, J.-J., Jiang, Y., Shi, X., Liu, C., Ma, Y., Luo, L., Mamtilahun, M., et al. (2022) · Theranostics · doi:10.7150/thno.68895 · Cited by 152 · see citing works
Designed proteins induce the formation of nanocage-containing extracellular vesicles
Votteler, J., Ogohara, C., Yi, S., Hsia, Y., Nattermann, U., Belnap, D. M., King, N. P., & Sundquist, W. I. (2016) · Nature · doi:10.1038/nature20607 · Cited by 149 · see citing works
He, R., Jiang, Y., Shi, Y., Liang, J., & Zhao, L. (2020) · Materials Science and Engineering C · doi:10.1016/j.msec.2020.111314 · Cited by 148 · see citing works
Exosome-associated AAV vector as a robust and convenient neuroscience tool
Hudry, E., Martin, C., Gandhi, S., György, B., Scheffer, D. I., Mu, D., Merkel, S. F., Mingozzi, F., Fitzpatrick, Z., Dimant, H., et al. (2016) · Gene Therapy · doi:10.1038/gt.2016.11 · Cited by 146 · see citing works
Ma, J., Zhang, S., Liu, J., Liu, F., Du, F., Li, M., Chen, A. T., Bao, Y., Suh, H., Avery, J., et al. (2019) · Small · doi:10.1002/smll.201902011 · Cited by 141 · see citing works
Ren, X., Zhao, Y., Xue, F., Zheng, Y., Huang, H., Wang, W., Chang, Y., Yang, H., & Zhang, J. (2019) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2019.07.008 · Cited by 139 · see citing works
Casella, G., Colombo, F., Finardi, A., Descamps, H., Ill-Raga, G., Spinelli, A., Podini, P., Bastoni, M., Martino, G., Muzio, L., et al. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2018.06.024 · Cited by 134 · see citing works
Xin, H., Liu, Z., Buller, B., Li, Y., Golembieski, W., Gan, X., Wang, F., Lü, M., Ali, M. M., Zhang, Z. G., et al. (2020) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x20950489 · Cited by 132 · see citing works
Xin, H., Sha, X., Jiang, X., Chen, L., Law, K., Gu, J., Chen, Y., Wang, X., & Fang, X. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.11.018 · Cited by 131 · see citing works
Oh, S. K. W., Kim, B. J., Singh, N. P., Lai, H. C., & Sasaki, T. (2008) · Cancer Letters · doi:10.1016/j.canlet.2008.08.031 · Cited by 131 · see citing works
Recent progresses in exosome-based systems for targeted drug delivery to the brain
Bashyal, S., Chhitij, T., & Lee, S. K. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.06.011 · Cited by 129 · see citing works
Wang, S., Jia, J., & Wang, Z. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170848 · Cited by 128 · see citing works
Goh, W. J., Lee, C. K., Zou, S., Woon, E. C. Y., Czarny, B., & Pastorin, G. (2017) · International Journal of Nanomedicine · doi:10.2147/ijn.s131786 · Cited by 122 · see citing works
Zhang, C., Song, J., Lou, L., Qi, X., Zhao, L., Fan, B., Sun, G., Lv, Z., Fan, Z., Jiao, B., et al. (2020) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10203 · Cited by 109 · see citing works
Human neural stem cell-derived extracellular vesicles mitigate hallmarks of Alzheimer’s disease
Apodaca, L. A., Baddour, A. A. D., Garcia, C., Alikhani, L., Giedzinski, E., Ru, N., Agrawal, A., Acharya, M. M., & Baulch, J. E. (2021) · Alzheimer s Research & Therapy · doi:10.1186/s13195-021-00791-x · Cited by 109 · see citing works
Sha, S., Shen, X., Cao, Y., & Qu, L. (2021) · Aging · doi:10.18632/aging.203088 · Cited by 109 · see citing works
Han, L., Li, J., Huang, S., Huang, R., Liu, S., Hu, X., Yi, P., Shan, D., Wang, X., Lei, H. C., et al. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.01.005 · Cited by 107 · see citing works
Raffaele, S., Gelosa, P., Bonfanti, E., Lombardi, M., Castiglioni, L., Cimino, M., Sironi, L., Abbracchio, M. P., Verderio, C., & Fumagalli, M. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.12.009 · Cited by 106 · see citing works
Han, Y., Seyfried, D., Meng, Y., Yang, D., Schultz, L. R., Chopp, M., & Seyfried, D. M. (2018) · Journal of neurosurgery · doi:10.3171/2018.2.jns171475 · Cited by 105 · see citing works
Ma, Y., Li, C., Huang, Y., Wang, Y., Xia, X., & Zheng, J. (2019) · Cell Communication and Signaling · doi:10.1186/s12964-019-0418-3 · Cited by 105 · see citing works
Xue, C., Li, X., Ba, L., Zhang, M., Yang, Y., Gao, Y., Sun, Z., Han, Q., & Zhao, R. C. (2021) · Aging and disease · doi:10.14336/ad.2020.1221 · Cited by 100 · see citing works
Neural Stem Cell-Derived Exosomes Regulate Neural Stem Cell Differentiation Through miR-9-Hes1 Axis
Yuan, P., Ding, L., Chen, H., Wang, Y., Li, C., Zhao, S., Yang, X., Ma, Y., Zhu, J., Qi, X., et al. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.601600 · Cited by 92 · see citing works
Kim, M., Kim, G., Hwang, D. W., & Lee, M. (2019) · Journal of Biomedical Nanotechnology · doi:10.1166/jbn.2019.2866 · Cited by 90 · see citing works
Kuroda, H., Tachikawa, M., Yagi, Y., Umetsu, M., Nurdin, A., Miyauchi, E., Watanabe, M., Uchida, Y., & Terasaki, T. (2018) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.8b00985 · Cited by 85 · see citing works
Gao, G., Zhao, S., Xia, X., Li, C., Li, C., Ji, C., Sheng, S., Tang, Y., Zhu, J., Wang, Y., et al. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00264 · Cited by 85 · see citing works
Garg, T., Bhandari, S., Rath, G., & Goyal, A. K. (2015) · Journal of drug targeting · doi:10.3109/1061186x.2015.1029930 · Cited by 84 · see citing works
Li, X., Zhang, Y., Wang, Y., Zhao, D., Sun, C., Zhou, S.-T., Xu, D., & Zhao, J. (2020) · Neural Plasticity · doi:10.1155/2020/8814239 · Cited by 82 · see citing works
Exosomes as Targeted Delivery Platform of CRISPR/Cas9 for Therapeutic Genome Editing
Duan, L., Ouyang, K., Wang, J., Xu, L., Xu, X., Wen, C., Xie, Y., Liang, Y., & Xia, J. (2021) · ChemBioChem · doi:10.1002/cbic.202100359 · Cited by 82 · see citing works
Self-citationLi, Z., Zhou, X., Gao, X., Bai, D., Dong, Y., Sun, W., Zhao, L., Wei, M., Yang, X., Yang, G., et al. (2020) · Journal of Extracellular Vesicles · doi:10.1080/20013078.2020.1816710 · Cited by 81 · see citing works
Native and Bioengineered Exosomes for Ischemic Stroke Therapy
Khan, H. L., Pan, J., Li, Y.-F., Zhang, Z., & Yang, G. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.619565 · Cited by 79 · see citing works
Jiang, W., Ma, P., Deng, L., Liu, Z., Wang, X., Liu, X., & Long, G. (2020) · Journal of Extracellular Vesicles · doi:10.1080/20013078.2020.1716513 · Cited by 74 · see citing works
Wu, J., Li, Y., Wang, J., Hu, X.-B., Huang, S. Q., Luo, S., & Xiang, D. (2021) · Journal of Nanobiotechnology · doi:10.1186/s12951-021-01153-3 · Cited by 73 · see citing works
Self-citationDelivery of siRNA based on engineered exosomes for glioblastoma therapy by targeting STAT3
Liang, S., Zuo, F.-F., Yin, B., & Ye, B. (2022) · Biomaterials Science · doi:10.1039/d1bm01723c · Cited by 73 · see citing works
Liang, Y., Iqbal, Z., Wang, J., Xu, L., Xu, X., Ouyang, K., Zhang, H., Lu, J., Duan, L., & Xia, J. (2022) · Biomaterials Science · doi:10.1039/d2bm00480a · Cited by 72 · see citing works
Self-citationDrug Delivery across the Blood–Brain Barrier
Khawli, L. A., & Prabhu, S. (2013) · Molecular Pharmaceutics · doi:10.1021/mp400170b · Cited by 71 · see citing works
Luo, L., Zang, G., Liu, B., Qin, X., Zhang, Y., Chen, Y., Zhang, H., Wu, W., & Wang, G. (2021) · Theranostics · doi:10.7150/thno.60785 · Cited by 71 · see citing works
Self-citationBiodistribution and Pharmacokinectics of Liposomes and Exosomes in a Mouse Model of Sepsis
Mirzaaghasi, A., Han, Y., Ahn, S., Choi, C., & Park, J. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13030427 · Cited by 70 · see citing works
The glucose transporter and blood‐brain barrier of human brain tumors
Guérin, C. J., Laterra, J., Hruban, R. H., et al. (1990) · Annals of Neurology · doi:10.1002/ana.410280606 · Cited by 69 · see citing works
Liu, M., Hu, Y., & Chen, G. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.01453 · Cited by 67 · see citing works
Perets, N., Oron, O., Herman, S., Elliott, E., & Offen, D. (2020) · Molecular Autism · doi:10.1186/s13229-020-00366-x · Cited by 64 · see citing works
Brain Targeted Drug Delivery System
(2018) · Elsevier eBooks · doi:10.1016/c2017-0-00836-4 · Cited by 62 · see citing works
Use of a Hollow Fiber Bioreactor to Collect Extracellular Vesicles from Cells in Culture
Yan, I. K., Shukla, N., Borrelli, D. A., & Patel, T. C. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-7652-2_4 · Cited by 61 · see citing works
Mesenchymal Stem Cell-Derived Exosomes for Treatment of Autism Spectrum Disorder
Liang, Y., Duan, L., Xu, X. G., Li, X., Liu, M., Chen, H., Lu, J., & Xia, J. (2020) · ACS Applied Bio Materials · doi:10.1021/acsabm.0c00831 · Cited by 61 · see citing works
Self-citationZhang, R., Fu, Y., Cheng, M., Ma, W., Zheng, N., Wang, Y., & Wu, Z. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.10.009 · Cited by 61 · see citing works
Glioma-derived exosomes hijack the blood–brain barrier to facilitate nanocapsule delivery via LCN2
Yang, C., Wu, Y., Wang, L., Li, S., Zhou, J., Tan, Y., Song, J. L., Xing, H., Yi, K., Zhan, Q., et al. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.03.038 · Cited by 61 · see citing works
Haney, M. J., Suresh, P., Zhao, Y., Kanmogne, G. D., Kadiu, I., Sokolsky‐Papkov, M., Klyachko, N. L., Mosley, R. L., Kabanov, A. V., Gendelman, H. E., et al. (2012) · Nanomedicine · doi:10.2217/nnm.11.156 · Cited by 58 · see citing works
Membrane-Decorated Exosomes for Combination Drug Delivery and Improved Glioma Therapy
Liang, S., Xu, H., & Ye, B. (2021) · Langmuir · doi:10.1021/acs.langmuir.1c02500 · Cited by 55 · see citing works
Zhou, S.-T., Gao, B., Sun, C., Bai, Y., Cheng, D., Zhang, Y., Li, X., Zhao, J., & Xu, D. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.05.046 · Cited by 50 · see citing works
Reynolds, J. L., & Mahajan, S. D. (2019) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-019-09895-6 · Cited by 49 · see citing works
Orefice, N. S., Souchet, B., Braudeau, J., Alves, S., Piguet, F., Collaud, F., Ronzitti, G., Tada, S., Hantraye, P., Mingozzi, F., et al. (2019) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2019.06.005 · Cited by 48 · see citing works
Exosome-Mediated Drug Delivery for Cell-Free Therapy of Osteoarthritis
Duan, L., Xu, X. G., Xu, L., et al. (2020) · Current Medicinal Chemistry · doi:10.2174/0929867327666201118161232 · Cited by 35 · see citing works
Self-citationReprogramming Extracellular Vesicles for Protein Therapeutics Delivery
Ovchinnikova, L. A., Terekhov, S. S., Ziganshin, R., Bagrov, D. V., Filimonova, I. N., Zalevsky, A. O., & Lomakin, Y. A. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13060768 · Cited by 31 · see citing works
BMI1 regulates multiple myeloma-associated macrophage’s pro-myeloma functions
Zhang, D., Huang, J., Wang, F., Ding, H., Cui, Y., Yang, Y., Xu, J., Luo, H., Gao, Y., Pan, L., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03748-y · Cited by 30 · see citing works
Guo, L., Pan, J., Li, F., Zhao, L., & Shi, Y. (2021) · IET Nanobiotechnology · doi:10.1049/nbt2.12003 · Cited by 29 · see citing works
Mesenchymal Stromal Cells-Derived Exosome and the Roles in the Treatment of Traumatic Brain Injury
Mot, Y. Y., Moses, E. J., Yusoff, N. M., Ling, K., Yong, Y. K., & Tan, J. J. (2022) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-022-01201-y · Cited by 29 · see citing works
Human Brain Disorders: A Review
Naz, F., & Siddique, Y. H. (2020) · The Open Biology Journal · doi:10.2174/1874196702008010006 · Cited by 28 · see citing works
Wang, Y., Wang, D., & Guo, D. (2016) · PLOS ONE · doi:10.1371/journal.pone.0146646 · Cited by 23 · see citing works
Parga, J. A., García-Garrote, M., Martı́nez, S., Raya, Á., Labandeira-García, J. L., & Rodríguez‐Pallares, J. (2017) · Molecular Neurobiology · doi:10.1007/s12035-017-0681-5 · Cited by 23 · see citing works
Erratum: Exosome-associated AAV vector as a robust and convenient neuroscience tool
Hudry, E., Martin, C. A., Gandhi, S., et al. (2016) · Gene Therapy · doi:10.1038/gt.2016.65 · Cited by 19 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [126]Mo J. Li M. Zinc sulfide-based hybrid exosome-coated autophagic flux-mediated hydrogen sulfide-sensitized PDT/chemotherapeutic synergistic nanoplatform for targeted treatment of glioblastoma stem-like cells in orthotopic mouse glioblastoma model Preprint at bioRxiv 2020
Cited by
Sorted by citations
Liu, Q., Li, D., Pan, X., & Liang, Y. (2023) · Journal of Nanobiotechnology · doi:10.1186/s12951-023-02081-0 · Cited by 201 · see citing works
Self-citationExosome for mRNA delivery: Strategies and therapeutic applications
Iqbal, Z., Rehman, K., Mahmood, A., Shabbir, M., Liang, Y., Duan, L., & Zeng, H. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02634-x · Cited by 144 · see citing works
Self-citationProgramming assembly of biomimetic exosomes: An emerging theranostic nanomedicine platform
Xu, X., Xu, L., Wen, C., Xia, J., Zhang, Y., & Liang, Y. (2023) · Materials Today Bio · doi:10.1016/j.mtbio.2023.100760 · Cited by 101 · see citing works
Self-citationXu, X., Iqbal, Z., Xu, L., Wen, C., Duan, L., Xia, J., Yang, N., Zhang, Y., & Liang, Y. (2024) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.13610 · Cited by 68 · see citing works
Self-citationOsteoclast-targeted delivery of anti-miRNA oligonucleotides by red blood cell extracellular vesicles
Xu, L., Xu, X., Liang, Y., Wen, C., Ouyang, K., Huang, J., Xiao, Y., Deng, X., Xia, J., & Duan, L. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.04.043 · Cited by 65 · see citing works
Self-citationYue, N.-N., Xu, H.-M., Xu, J., Zhu, M.-Z., Zhang, Y., Tian, C.-M., Nie, Y.-Q., Yao, J., Liang, Y.-J., Li, D.-F., et al. (2023) · International Journal of Nanomedicine · doi:10.2147/ijn.s413141 · Cited by 46 · see citing works
Self-citationNájera-Maldonado, L., Parra-González, M., Peralta-Cuevas, E., Gutierrez-Onofre, A. J., Garcia-Atutxa, I., & Villanueva-Flores, F. (2025) · Pharmaceutics · doi:10.3390/pharmaceutics17091169 · Cited by 40 · see citing works
Sun, W. Y., Lee, D.-S., Park, J. H., Kim, O.-H., Choi, H. J., & Kim, S.-J. (2025) · Journal of Breast Cancer · doi:10.4048/jbc.2024.0262 · Cited by 12 · see citing works
- Authors
- Liang, Y., Iqbal, Z., Lu, J., Wang, J., Zhang, H., Chen, X., Duan, L., & Xia, J.
- Affiliations
- Shenzhen University (CN)
- Shenzhen KangNing Hospital (CN)
- State Key Laboratory of Digital Medical Engineering (CN)
- Chinese University of Hong Kong (HK)
- Corresponding author
- Duan, Li
- Xia, Jiang
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2023-05
- Volume
- 31
- Issue
- 5
- Pages
- 1207-1224
- ISSN
- 1525-0016 (ISSN-L)
- PMC
- PMC10188644
- OpenAlex
- W4306393265
- Cited by
- 162
- References
- 146
- Citations by year
- 2026: 31 · 2025: 54 · 2024: 44 · 2023: 33
- FWCI
- 3.41
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Innovation and Technology Commission
- Shenzhen Science and Technology Innovation Committee
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- brain drug delivery, extracellular vesicles, exosomes, exosome engineering, blood-brain barrier, neurological disorders
- MeSH terms
- Extracellular Vesicles, Blood-Brain Barrier, Brain, Drug Delivery Systems, Exosomes
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
