최태현 (서울대학교)

한빛사논문

조회198

최태현Choi Tae Hyeon

서울대학교

J. Nanobiotechnol., Feb 29 2024, 22 (1) 83 | https://doi.org/10.1186/s12951-024-02325-7 Development of finely tuned liposome nanoplatform for macrophage depletion

Tae Hyeon Choi^1,2†, Ran Ji Yoo^1,3,4†, Ji Yong Park^1,5, Ji Yoon Kim^1,5, Young Chan Ann^1,6, Jeongbin Park², Jin Sil Kim¹, Kyuwan Kim¹, Yu Jin Shin^1,7,8, Yong Jin Lee⁹, Kyo Chul Lee⁹, Jisu Park^7,8,10, Hyewon Chung^7,8,10, Seung Hyeok Seok^7,8,10, Hyung‑Jun Im^2,5,7* and Yun‑Sang Lee^1,3,5,7,8*

¹Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, South Korea.

²Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology,Seoul National University, Seoul 08826, South Korea.

³Department of Nuclear Medicine, Seoul National University Hospital, 101 Daehak‑Ro, Jongno‑Gu,Seoul, South Korea.

⁴Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.

⁵Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul, South Korea.

⁶School of Dentistry, Seoul National University, Seoul, South Korea.

⁷Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.

⁸Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.

⁹Division of Applied RI, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul, South Korea.

¹⁰Department of Microbiology and Immunology, and Institute of Endemic Disease, Seoul National University College of Medicine, Seoul, South Korea.

^†Tae Hyeon Choi and Ran Ji Yoo have contributed equally.

^*Correspondence: Hyung‑Jun Im, Yun‑Sang Lee

Abstract

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. 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-N ₃ and radiolabeling. Functionalization with Man-N ₃ 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 ^®. 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.

논문정보

형식Research article
게재일2024년 02월 (BRIC 등록일 2024-03-11)
연구진국내 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

댓글 작성 로그인

CV 열람하기

연락처 보기