Development of finely tuned liposome nanoplatform for macrophage depletion
Abstract Background Immunotherapy with clodronate-encapsulated liposomes, which induce macrophage depletion, has been studied extensively. However, previously reported liposomal formulation-based drugs (Clodrosome® and m-Clodrosome®) are limited by their inconsistent size and therapeutic efficacy. T...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-024-02325-7 |
| _version_ | 1797273391294578688 |
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| author | Tae Hyeon Choi Ran Ji Yoo Ji Yong Park Ji Yoon Kim Young Chan Ann Jeongbin Park Jin Sil Kim Kyuwan Kim Yu Jin Shin Yong Jin Lee Kyo Chul Lee Jisu Park Hyewon Chung Seung Hyeok Seok Hyung-Jun Im Yun-Sang Lee |
| author_facet | Tae Hyeon Choi Ran Ji Yoo Ji Yong Park Ji Yoon Kim Young Chan Ann Jeongbin Park Jin Sil Kim Kyuwan Kim Yu Jin Shin Yong Jin Lee Kyo Chul Lee Jisu Park Hyewon Chung Seung Hyeok Seok Hyung-Jun Im Yun-Sang Lee |
| author_sort | Tae Hyeon Choi |
| collection | DOAJ |
| description | Abstract Background Immunotherapy with clodronate-encapsulated liposomes, which induce macrophage depletion, has been studied extensively. However, previously reported liposomal formulation-based drugs (Clodrosome® and m-Clodrosome®) are limited by their inconsistent size and therapeutic efficacy. Thus, we aimed to achieve consistent therapeutic effects by effectively depleting macrophages with uniform-sized liposomes. Results We developed four types of click chemistry-based liposome nanoplatforms that were uniformly sized and encapsulated with clodronate, for effective macrophage depletion, followed by conjugation with Man-N3 and radiolabeling. Functionalization with Man-N3 improves the specific targeting of M2 macrophages, and radioisotope labeling enables in vivo imaging of the liposome nanoplatforms. The functionalized liposome nanoplatforms are stable under physiological conditions. The difference in the biodistribution of the four liposome nanoplatforms in vivo were recorded using positron emission tomography imaging. Among the four platforms, the clodronate-encapsulated mannosylated liposome effectively depleted M2 macrophages in the normal liver and tumor microenvironment ex vivo compared to that by Clodrosome® and m-Clodrosome®. Conclusion The newly-developed liposome nanoplatform, with finely tuned size control, high in vivo stability, and excellent ex vivo M2 macrophage targeting and depletion effects, is a promising macrophage-depleting agent. Graphical Abstract |
| first_indexed | 2024-03-07T14:42:43Z |
| format | Article |
| id | doaj.art-73dd56cc7faf45859548ae9a93d8c652 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-03-07T14:42:43Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-73dd56cc7faf45859548ae9a93d8c6522024-03-05T20:09:47ZengBMCJournal of Nanobiotechnology1477-31552024-02-0122111310.1186/s12951-024-02325-7Development of finely tuned liposome nanoplatform for macrophage depletionTae Hyeon Choi0Ran Ji Yoo1Ji Yong Park2Ji Yoon Kim3Young Chan Ann4Jeongbin Park5Jin Sil Kim6Kyuwan Kim7Yu Jin Shin8Yong Jin Lee9Kyo Chul Lee10Jisu Park11Hyewon Chung12Seung Hyeok Seok13Hyung-Jun Im14Yun-Sang Lee15Department of Nuclear Medicine, Seoul National University College of MedicineDepartment of Nuclear Medicine, Seoul National University College of MedicineDepartment of Nuclear Medicine, Seoul National University College of MedicineDepartment of Nuclear Medicine, Seoul National University College of MedicineDepartment of Nuclear Medicine, Seoul National University College of MedicineDepartment of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National UniversityDepartment of Nuclear Medicine, Seoul National University College of MedicineDepartment of Nuclear Medicine, Seoul National University College of MedicineDepartment of Nuclear Medicine, Seoul National University College of MedicineDivision of Applied RI, Korea Institute of Radiological and Medical Sciences (KIRAMS)Division of Applied RI, Korea Institute of Radiological and Medical Sciences (KIRAMS)Cancer Research Institute, Seoul National University College of MedicineCancer Research Institute, Seoul National University College of MedicineCancer Research Institute, Seoul National University College of MedicineDepartment of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National UniversityDepartment of Nuclear Medicine, Seoul National University College of MedicineAbstract Background Immunotherapy with clodronate-encapsulated liposomes, which induce macrophage depletion, has been studied extensively. However, previously reported liposomal formulation-based drugs (Clodrosome® and m-Clodrosome®) are limited by their inconsistent size and therapeutic efficacy. Thus, we aimed to achieve consistent therapeutic effects by effectively depleting macrophages with uniform-sized liposomes. Results We developed four types of click chemistry-based liposome nanoplatforms that were uniformly sized and encapsulated with clodronate, for effective macrophage depletion, followed by conjugation with Man-N3 and radiolabeling. Functionalization with Man-N3 improves the specific targeting of M2 macrophages, and radioisotope labeling enables in vivo imaging of the liposome nanoplatforms. The functionalized liposome nanoplatforms are stable under physiological conditions. The difference in the biodistribution of the four liposome nanoplatforms in vivo were recorded using positron emission tomography imaging. Among the four platforms, the clodronate-encapsulated mannosylated liposome effectively depleted M2 macrophages in the normal liver and tumor microenvironment ex vivo compared to that by Clodrosome® and m-Clodrosome®. Conclusion The newly-developed liposome nanoplatform, with finely tuned size control, high in vivo stability, and excellent ex vivo M2 macrophage targeting and depletion effects, is a promising macrophage-depleting agent. Graphical Abstracthttps://doi.org/10.1186/s12951-024-02325-7LiposomeMacrophageClodronateMolecular imagingClick chemistry |
| spellingShingle | Tae Hyeon Choi Ran Ji Yoo Ji Yong Park Ji Yoon Kim Young Chan Ann Jeongbin Park Jin Sil Kim Kyuwan Kim Yu Jin Shin Yong Jin Lee Kyo Chul Lee Jisu Park Hyewon Chung Seung Hyeok Seok Hyung-Jun Im Yun-Sang Lee Development of finely tuned liposome nanoplatform for macrophage depletion Journal of Nanobiotechnology Liposome Macrophage Clodronate Molecular imaging Click chemistry |
| title | Development of finely tuned liposome nanoplatform for macrophage depletion |
| title_full | Development of finely tuned liposome nanoplatform for macrophage depletion |
| title_fullStr | Development of finely tuned liposome nanoplatform for macrophage depletion |
| title_full_unstemmed | Development of finely tuned liposome nanoplatform for macrophage depletion |
| title_short | Development of finely tuned liposome nanoplatform for macrophage depletion |
| title_sort | development of finely tuned liposome nanoplatform for macrophage depletion |
| topic | Liposome Macrophage Clodronate Molecular imaging Click chemistry |
| url | https://doi.org/10.1186/s12951-024-02325-7 |
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