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- Title
Development of finely tuned liposome nanoplatform for macrophage depletion.
- Authors
Choi, Tae Hyeon; Yoo, Ran Ji; Park, Ji Yong; Kim, Ji Yoon; Ann, Young Chan; Park, Jeongbin; Kim, Jin Sil; Kim, Kyuwan; Shin, Yu Jin; Lee, Yong Jin; Lee, Kyo Chul; Park, Jisu; Chung, Hyewon; Seok, Seung Hyeok; Im, Hyung-Jun; Lee, Yun-Sang
- 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.
- Subjects
LIPOSOMES; POSITRON emission tomography; MACROPHAGES
- Publication
Journal of Nanobiotechnology, 2024, Vol 22, Issue 1, p1
- ISSN
1477-3155
- Publication type
Article
- DOI
10.1186/s12951-024-02325-7