Fusogenic lipid nanoparticles for rapid delivery of large therapeutic molecules to exosomes
Abstract Exosomes, as cell-derived lipid nanoparticles, are promising drug carriers because they can traverse challenging physiological barriers such as the blood-brain barrier (BBB). However, a major obstacle in utilizing exosomes as drug carriers is loading large therapeutic molecules without comp...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59489-5 |
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| author | Gamsong Son Jiyoung Song Jae Chul Park Hong Nam Kim Hojun Kim |
| author_facet | Gamsong Son Jiyoung Song Jae Chul Park Hong Nam Kim Hojun Kim |
| author_sort | Gamsong Son |
| collection | DOAJ |
| description | Abstract Exosomes, as cell-derived lipid nanoparticles, are promising drug carriers because they can traverse challenging physiological barriers such as the blood-brain barrier (BBB). However, a major obstacle in utilizing exosomes as drug carriers is loading large therapeutic molecules without compromising the structural integrity of embedded biomolecules. Here, we introduce a membrane fusion method utilizing fusogenic lipid nanoparticles, cubosomes, to load large molecules into exosomes in a non-destructive manner. When the drug-loaded cubosome and exosome solutions are simply mixed, membrane fusion is completed in just 10 min. Our method effectively loads doxorubicin and immunoglobulin G into exosomes. Moreover, even the most challenging molecule—mRNA—is loaded with nearly 100% efficiency, demonstrating the versatility of our approach. In terms of biological behavior, the resulting hybrid exosomes preserve the functional behavior of exosomes in BBB uptake and penetration. Surprisingly, controlling exosome-to-cubosome ratios allows precise control over BBB uptake and transport. Furthermore, these hybrid exosomes retain cell-specific delivery properties, preserving the targeted delivery functions dictated by their exosomal origin. This study demonstrates the feasibility of a mix-and-load method for rapid and efficient drug loading into exosomes, with significant potential for the treatment of neurological diseases. |
| format | Article |
| id | doaj-art-aaa14aa9521f41f0b49373459df28552 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-aaa14aa9521f41f0b49373459df285522025-08-20T02:34:03ZengNature PortfolioNature Communications2041-17232025-05-0116111510.1038/s41467-025-59489-5Fusogenic lipid nanoparticles for rapid delivery of large therapeutic molecules to exosomesGamsong Son0Jiyoung Song1Jae Chul Park2Hong Nam Kim3Hojun Kim4Division of Bio-Medical Science &Technology, KIST School, University of Science and TechnologyBrain Science Institute, Korea Institute of Science and Technology (KIST)Center for Advanced Biomolecular Recognition, Korea Institute of Science and Technology (KIST)Division of Bio-Medical Science &Technology, KIST School, University of Science and TechnologyDivision of Bio-Medical Science &Technology, KIST School, University of Science and TechnologyAbstract Exosomes, as cell-derived lipid nanoparticles, are promising drug carriers because they can traverse challenging physiological barriers such as the blood-brain barrier (BBB). However, a major obstacle in utilizing exosomes as drug carriers is loading large therapeutic molecules without compromising the structural integrity of embedded biomolecules. Here, we introduce a membrane fusion method utilizing fusogenic lipid nanoparticles, cubosomes, to load large molecules into exosomes in a non-destructive manner. When the drug-loaded cubosome and exosome solutions are simply mixed, membrane fusion is completed in just 10 min. Our method effectively loads doxorubicin and immunoglobulin G into exosomes. Moreover, even the most challenging molecule—mRNA—is loaded with nearly 100% efficiency, demonstrating the versatility of our approach. In terms of biological behavior, the resulting hybrid exosomes preserve the functional behavior of exosomes in BBB uptake and penetration. Surprisingly, controlling exosome-to-cubosome ratios allows precise control over BBB uptake and transport. Furthermore, these hybrid exosomes retain cell-specific delivery properties, preserving the targeted delivery functions dictated by their exosomal origin. This study demonstrates the feasibility of a mix-and-load method for rapid and efficient drug loading into exosomes, with significant potential for the treatment of neurological diseases.https://doi.org/10.1038/s41467-025-59489-5 |
| spellingShingle | Gamsong Son Jiyoung Song Jae Chul Park Hong Nam Kim Hojun Kim Fusogenic lipid nanoparticles for rapid delivery of large therapeutic molecules to exosomes Nature Communications |
| title | Fusogenic lipid nanoparticles for rapid delivery of large therapeutic molecules to exosomes |
| title_full | Fusogenic lipid nanoparticles for rapid delivery of large therapeutic molecules to exosomes |
| title_fullStr | Fusogenic lipid nanoparticles for rapid delivery of large therapeutic molecules to exosomes |
| title_full_unstemmed | Fusogenic lipid nanoparticles for rapid delivery of large therapeutic molecules to exosomes |
| title_short | Fusogenic lipid nanoparticles for rapid delivery of large therapeutic molecules to exosomes |
| title_sort | fusogenic lipid nanoparticles for rapid delivery of large therapeutic molecules to exosomes |
| url | https://doi.org/10.1038/s41467-025-59489-5 |
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