Engineering hybrid exosomes by membrane fusion with liposomes
Open accessAbstract
Exosomes are a valuable biomaterial for the development of novel nanocarriers as functionally advanced drug delivery systems. To control and modify the performance of exosomal nanocarriers, we developed hybrid exosomes by fusing their membranes with liposomes using the freeze–thaw method. Exosomes embedded with a specific membrane protein isolated from genetically modified cells were fused with various liposomes, confirming that membrane engineering methods can be combined with genetic modification techniques. Cellular uptake studies performed using the hybrid exosomes revealed that the interactions between the developed exosomes and cells could be modified by changing the lipid composition or the properties of the exogenous lipids. These results suggest that the membrane-engineering approach reported here offers a new strategy for developing rationally designed exosomes as hybrid nanocarriers for use in advanced drug delivery systems.
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?
Exosomes are highly efficient in delivering cargo to cells due to their unique transmembrane proteins that promote cell attachment and facilitate endocytosis.
“On the other hand, exosomes are highly efficient in delivering cargo to cells due to their unique transmembrane proteins that promote cell attachment and facilitate endocytosis [113].”
From Exosome for mRNA delivery: Strategies and therapeutic applications (2024) · cites this paper as [113]
Exosome-liposome hybrids have been shown to form structures larger than 200 nm.
“These exosome-liposome hybrids have been shown to form structures larger than 200 nm [113]”
From Exosome for mRNA delivery: Strategies and therapeutic applications (2024) · cites this paper as [113]
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
Valadi, H., Ekström, K., Bossios, A., Sjöstrand, M., Lee, J. J., & Lötvall, J. O. (2007) · Nature Cell Biology · doi:10.1038/ncb1596 · Cited by 12,834 · see citing works
Delivery 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
Liposomal drug delivery systems: From concept to clinical applications
Allen, T. M., & Cullis, P. R. (2013) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.09.037 · Cited by 4,839 · see citing works
Routes and mechanisms of extracellular vesicle uptake
Mulcahy, L. A., Pink, R. C., & Carter, D. R. F. (2014) · Journal of Extracellular Vesicles · doi:10.3402/jev.v3.24641 · Cited by 2,832 · 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
Vesicles of variable sizes produced by a rapid extrusion procedure
Mayer, L. D., Hope, M. J., & Cullis, P. R. (1986) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(86)90302-0 · Cited by 1,693 · see citing works
Systemically Injected Exosomes Targeted to EGFR Deliver Antitumor MicroRNA to Breast Cancer Cells
Ohno, S.-I., Takanashi, M., Sudo, K., Ueda, S., Ishikawa, A., Matsuyama, N., Fujita, K., Mizutani, T., Ohgi, T., Ochiya, T., et al. (2013) · Molecular Therapy · doi:10.1038/mt.2012.180 · Cited by 1,666 · see citing works
Microenvironmental pH Is a Key Factor for Exosome Traffic in Tumor Cells
Parolini, I., Federici, C., Raggi, C., Lugini, L., Palleschi, S., Milito, A. D., Coscia, C., Iessi, E., Logozzi, M., Molinari, A., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.041152 · Cited by 1,561 · see citing works
Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes
Montecalvo, A., Larregina, A. T., Shufesky, W. J., Stolz, D. B., Sullivan, M. L. G., Karlsson, J. M., Baty, C. J., Gibson, G. A., Erdös, G., Wang, Z., et al. (2011) · Blood · doi:10.1182/blood-2011-02-338004 · Cited by 1,380 · see citing works
Abuchowski, A., Es, T. V., Palczuk, N. C., & Davis, F. F. (1977) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)40291-2 · Cited by 1,358 · see citing works
Use of resonance energy transfer to monitor membrane fusion
Struck, D. K., Hoekstra, D., & Pagano, R. E. (1981) · Biochemistry · doi:10.1021/bi00517a023 · Cited by 1,281 · see citing works
Takahashi, Y., Nishikawa, M., Shinotsuka, H., Matsui, Y., Ohara, S., Imai, T., & Takakura, Y. (2013) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2013.03.013 · Cited by 729 · see citing works
Tian, T., Zhu, Y.-L., Zhou, Y.-Y., Liang, G.-F., Wang, Y.-Y., Hu, F.-H., & Xiao, Z.-D. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.588046 · Cited by 726 · see citing works
Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes
Wahlgren, J., Karlson, T. D. L., Brisslert, M., Sani, F. V., Telemo, E., Sunnerhagen, P., & Valadi, H. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks463 · Cited by 716 · see citing works
Johnsen, K. B., Gudbergsson, J. M., Skov, M. N., Pilgaard, L., Moos, T., & Duroux, M. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.04.005 · Cited by 704 · see citing works
Liposomes for the sustained drug release in vivo
Blume, G., & Cevc, G. (1990) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(90)90440-y · Cited by 701 · see citing works
Kooijmans, S. A. A., Stremersch, S., Braeckmans, K., de Smedt, S. C., Hendrix, A., Wood, M. J. A., Schiffelers, R. M., Raemdonck, K., & Vader, P. (2013) · Journal of Controlled Release · doi:10.1016/j.jconrel.2013.08.014 · Cited by 663 · see citing works
Systemic exosomal siRNA delivery reduced alpha‐synuclein aggregates in brains of transgenic mice
Cooper, J. A. D., Wiklander, O. P. B., Nordin, J. Z., Al‐Shawi, R., Wood, M. J. A., Vithlani, M., Schapira, A. H. V., Simons, J. P., Andaloussi, S. E., & Alvarez‐Erviti, L. (2014) · Movement Disorders · doi:10.1002/mds.25978 · Cited by 509 · see citing works
Exosomes are natural carriers of exogenous siRNA to human cells in vitro
Shtam, T. A., Kovalev, R. A., Varfolomeeva, E. Y., Makarov, E. M., Kil, Y. V., & Filatov, M. V. (2013) · Cell Communication and Signaling · doi:10.1186/1478-811x-11-88 · Cited by 499 · see citing works
Extracellular vesicles as drug delivery systems: Lessons from the liposome field
van der Meel, R., Fens, M. H. A. M., Vader, P., van Solinge, W. W., Eniola‐Adefeso, O., & Schiffelers, R. M. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.07.049 · Cited by 483 · see citing works
Differential fates of biomolecules delivered to target cells via extracellular vesicles
Kanada, M., Bachmann, M. H., Hardy, J., Frimannson, D. O., Bronsart, L., Wang, A., Sylvester, M. D., Schmidt, T. L., Kaspar, R., Butte, M., et al. (2015) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1418401112 · Cited by 442 · see citing works
Rudolph, A. S., & Crowe, J. H. (1985) · Cryobiology · doi:10.1016/0011-2240(85)90184-1 · Cited by 424 · see citing works
Exosomes: The Future of Biomarkers in Medicine
Properzi, F., Logozzi, M., & Fais, S. (2013) · Biomarkers in Medicine · doi:10.2217/bmm.13.63 · Cited by 392 · see citing works
Pick, U. (1981) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(81)90358-1 · Cited by 349 · see citing works
Dynamics of exosome internalization and trafficking
Tian, T., Zhu, Y., Hu, F., Wang, Y., Huang, N., & Xiao, Z. (2012) · Journal of Cellular Physiology · doi:10.1002/jcp.24304 · Cited by 340 · see citing works
Mineo, M., Garfield, S. H., Taverna, S., Flugy, A. M., Leo, G. D., Alessandro, R., & Kohn, E. C. (2011) · Angiogenesis · doi:10.1007/s10456-011-9241-1 · Cited by 267 · see citing works
Towards traceable size determination of extracellular vesicles
Varga, Z., Yuana, Y., Grootemaat, A. E., van der Pol, E., Gollwitzer, C., Krumrey, M. K., & Nieuwland, R. (2014) · Journal of Extracellular Vesicles · doi:10.3402/jev.v3.23298 · Cited by 243 · see citing works
Nagata, Y., Furugen, R., Hiasa, A., et al. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.3.1336 · Cited by 159 · see citing works
Lee, J.-S., Kim, J., Jeong, M., Lee, H., Goh, U., Kim, H., Kim, B., & Park, J.-H. (2015) · Nano letters (Print) · doi:10.1021/nl5047494 · Cited by 151 · see citing works
Freeze-Anneal-Thaw Cycling of Unilamellar Liposomes: Effect on Encapsulation Efficiency
Costa, A. P., Xu, X., & Burgess, D. J. (2013) · Pharmaceutical Research · doi:10.1007/s11095-013-1135-z · Cited by 141 · see citing works
Emerging technologies in extracellular vesicle-based molecular diagnostics
Jia, S., Zocco, D., Samuels, M., Chou, M. F., Chammas, R., Skog, J., Zarovni, N., Momen-Heravi, F., & Kuo, W. (2014) · Expert Review of Molecular Diagnostics · doi:10.1586/14737159.2014.893828 · Cited by 130 · see citing works
He, J., Banizs, A. B., Huang, T., Dryden, K. A., Berr, S. S., Stone, J. R., Nakamoto, R. K., & Shi, W. (2014) · International Journal of Nanomedicine · doi:10.2147/ijn.s64267 · Cited by 86 · see citing works
Oku, N., & MacDonald, R. C. (1983) · Biochemistry · doi:10.1021/bi00273a023 · Cited by 78 · see citing works
Direct integration of cell‐free‐synthesized connexin‐43 into liposomes and hemichannel formation
Moritani, Y., Nomura, S. M., Morita, I., et al. (2010) · FEBS Journal · doi:10.1111/j.1742-4658.2010.07736.x · Cited by 76 · see citing works
MacDonald, R. C., Jones, F. D., & Qui, R. (1994) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(94)90187-2 · Cited by 60 · see citing works
Lee, J., & Lentz, B. R. (1997) · Biochemistry · doi:10.1021/bi9622332 · Cited by 57 · see citing works
Recent advances in the HER2 targeted therapy of gastric cancer
Matsuoka, T. (2015) · World Journal of Clinical Cases · doi:10.12998/wjcc.v3.i1.42 · Cited by 52 · see citing works
Siow, L. F., Rades, T., & Lim, M. H. (2007) · Cryobiology · doi:10.1016/j.cryobiol.2007.08.002 · Cited by 45 · see citing works
MacDonald, R. I., & MacDonald, R. C. (1983) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(83)90299-7 · Cited by 41 · see citing works
Membrane fusion of pH-sensitive liposomes – a quantitative study using giant unilamellar vesicles
Trier, S., Henriksen, J. R., & Andresen, T. L. (2011) · Soft Matter · doi:10.1039/c1sm05818e · Cited by 34 · see citing works
Fluorescence Assays for Liposome Fusion
Düzgüneş, N. (2003) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(03)72015-1 · Cited by 30 · see citing works
Talsma, H., van Steenbergen, M. J., & Crommelin, D. J. A. (1991) · International Journal of Pharmaceutics · doi:10.1016/0378-5173(91)90309-c · Cited by 29 · see citing works
Mukai, K., Yasutomi, Y., Watanabe, M., et al. (2002) · Gene Therapy · doi:10.1038/sj.gt.3301707 · Cited by 25 · see citing works
MacDonald, R. I. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)61125-1 · Cited by 11 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Zhang, Y., Bi, J., Huang, J., Tang, Y., Du, S., & Li, P. (2020) · International Journal of Nanomedicine · doi:10.2147/ijn.s264498 · Cited by 1,323 · see citing works
Surface 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
Advances in therapeutic applications of extracellular vesicles
Wiklander, O. P. B., Brennan, M. Á., Lötvall, J., Breakefield, X. O., & EL Andaloussi, S. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aav8521 · Cited by 1,039 · see citing works
Tumor exosome-based nanoparticles are efficient drug carriers for chemotherapy
Yong, T., Zhang, X., Bie, N., Zhang, H., Zhang, X., Li, F., Hakeem, A., Hu, J., Gan, L., Santos, H. A., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11718-4 · Cited by 806 · 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
Macrophage-derived exosome-mimetic hybrid vesicles for tumor targeted drug delivery
Rayamajhi, S., Nguyen, T. D. T., Marasini, R., & Aryal, S. (2019) · Acta Biomaterialia · doi:10.1016/j.actbio.2019.05.054 · Cited by 429 · see citing works
Extracellular vesicles: A bright star of nanomedicine
Wu, P., Zhang, B., Ocansey, D. K. W., Xu, W., & Qian, H. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2020.120467 · Cited by 368 · see citing works
Approaches to surface engineering of extracellular vesicles
Richter, M., Vader, P., & Fuhrmann, G. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.03.020 · Cited by 258 · see citing works
Exosome-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
Mehryab, F., Rabbani, S., Shahhosseini, S., Shekari, F., Fatahi, Y., Baharvand, H., & Haeri, A. (2020) · Acta Biomaterialia · doi:10.1016/j.actbio.2020.06.036 · Cited by 216 · see citing works
Current Strategies to Enhance Delivery of Drugs across the Blood–Brain Barrier
Teleanu, R. I., Preda, M. D., Niculescu, A.-G., Vladâcenco, O., Radu, C. I., Grumezescu, A. M., & Teleanu, D. M. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14050987 · Cited by 200 · see citing works
Chen, T., He, B., Tao, J., He, Y., Deng, H., Wang, X., & Zheng, Y. (2019) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2019.04.009 · Cited by 186 · see citing works
Exosomes as bio-inspired nanocarriers for RNA delivery: preparation and applications
Amiri, A., Bagherifar, R., Ansari Dezfouli, E., Kiaie, S. H., Jafari, R., & Ramezani, R. (2022) · Journal of Translational Medicine · doi:10.1186/s12967-022-03325-7 · Cited by 186 · see citing works
Wang, J., Zhu, M., & Nie, G. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.113974 · Cited by 153 · see citing works
Recent Advances in Exosome-Based Drug Delivery for Cancer Therapy
Kim, H., Jang, H., Cho, H., Choi, J., Hwang, K. Y., Choi, Y., Kim, S. H., & Yang, Y. (2021) · Cancers · doi:10.3390/cancers13174435 · Cited by 152 · see citing works
Exosome 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
Strategies for the use of Extracellular Vesicles for the Delivery of Therapeutics
Sil, S., Dagur, R. S., Liao, K., Peeples, E. S., Hu, G., Periyasamy, P., & Buch, S. (2020) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-019-09873-y · Cited by 109 · see citing works
Programming 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
Current advances in non‐viral gene delivery systems: Liposomes versus extracellular vesicles
Belhadj, Z., Qie, Y., Carney, R. P., Li, Y., & Nie, G. (2023) · BMEMat · doi:10.1002/bmm2.12018 · Cited by 79 · see citing works
Si, K., Dai, Z., Li, Z., Ye, Z., Ding, B., Feng, S., Sun, B., Shen, Y., & Xiao, Z. (2023) · Cytotherapy · doi:10.1016/j.jcyt.2023.01.005 · Cited by 60 · see citing works
Emerging prospects of extracellular vesicles for brain disease theranostics
Wang, R., Wang, X., Zhang, Y., Zhao, H., Cui, J., Li, J., & Di, L. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.12.024 · Cited by 48 · see citing works
MSC-Exos: important active factor of bone regeneration
Ren, S., Lin, Y., Liu, W., Yang, L., & Zhao, M. (2023) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2023.1136453 · Cited by 37 · see citing works
Exosomes and Biomaterials: In Search of a New Therapeutic Strategy for Multiple Sclerosis
Ojeda-Hernández, D. D., Hernández-Sapiéns, M. A., Reza-Zaldívar, E. E., Canales-Aguirre, A., Matías-Guiu, J. A., Matías-Guiu, J., Mateos-Díaz, J. C., Gómez-Pinedo, U., & Sancho-Bielsa, F. (2022) · Life · doi:10.3390/life12091417 · Cited by 25 · see citing works
Extracellular vesicle therapy for obesity-induced NAFLD: a comprehensive review of current evidence
Zhang, J., Ma, B., Wang, Z., Chen, Y., Li, C., & Dong, Y. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-023-01292-0 · Cited by 17 · see citing works
Ghosh, S., & Ghosh, S. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.878058 · Cited by 13 · see citing works
Extracellular Vesicles and Their Interplay with Biological Membranes
Yeo Xian Ping, J., Raj Neupane, Y., & Pastorin, G. (2022) · Physiology · doi:10.5772/intechopen.101297 · Cited by 9 · see citing works
- Authors
- Sato, Y. T., Umezaki, K., Sawada, S., Mukai, S.-A., Sasaki, Y., Harada, N., Shiku, H., & Akiyoshi, K.
- Affiliations
- Kyoto University (JP)
- Mie University (JP)
- Corresponding author
- Akiyoshi, Kazunari
- Venue
- Scientific Reports
- Published
- 2016-02-25
- Volume
- 6
- Issue
- 1
- Pages
- 21933-21933
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4766490
- OpenAlex
- W2406609064
- Cited by
- 744
- References
- 44
- Citations by year
- 2026: 67 · 2025: 101 · 2024: 108 · 2023: 118 · 2022: 102 · 2021: 89 · 2020: 66 · 2019: 34 · 2018: 35 · 2017: 18 · 2016: 5
- FWCI
- 15.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion, cc-by)
- Funders
- Japan Science and Technology Agency
- Exploratory Research for Advanced Technology
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- membrane fusion, liposomes, membrane engineering, drug delivery systems, cellular uptake, lipid composition, genetically modified cells, exogenous lipids
- MeSH terms
- RAW 264.7 Cells, Animals, Flow Cytometry, Fluorescent Dyes, Freezing, HeLa Cells, Humans, Liposomes, Membrane Fusion, Blotting, Western, Microscopy, Confocal, Erb-b2 Receptor Tyrosine Kinases, Fluorescence Resonance Energy Transfer, Mice, Nanoparticles, 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