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Abstract
The development of molecular imaging probes to identify key cellular changes within lung metastases may lead to noninvasive detection of metastatic lesions in the lung. In this study, we constructed a macrophage-targeted clickable albumin nanoplatform (CAN) decorated with mannose as the targeting ligand using a click reaction to maintain the intrinsic properties of albumin in vivo. We also modified the number of mannose molecules on the CAN and found that mannosylated serum albumin (MSA) harboring six molecules of mannose displayed favorable pharmacokinetics that allowed high-contrast imaging of the lung, rendering it suitable for in vivo visualization of lung metastases. Due to the optimized control of functionalization and surface modification, MSA enhanced blood circulation time and active/passive targeting abilities and was specifically incorporated by mannose receptor (CD206)-expressing macrophages in the metastatic lung. Moreover, extensive in vivo imaging studies using single-photon emission computed tomography (SPECT)/CT and positron emission tomography (PET) revealed that blood circulation of time-optimized MSA can be used to discern metastatic lesions, with a strong correlation between its signal and metastatic burden in the lung.

알부민 나노플랫폼을 활용하여 종양 마크로파지에 선택적으로 반응해 신호를 발생시킬 수 있는 이미지 프로브를 개발하였으며, 이를 이용하여 비침습적 폐 전이 진단 가능성을 검증하였음

Affiliations

Hyewon Chung 1 2, Ji Yong Park 3 4 5 6, Kyuwan Kim 4 5, Ran Ji Yoo 4 5, Minseok Suh 7, Gyo Jeong Gu 1, Jin Sil Kim 4, Tae Hyeon Choi 4 7, Jung Woo Byun 4, Young Wook Ju 8, Wonshik Han 8, Han Suk Ryu 9, Gehoon Chung 6 10, Do Won Hwang 4 11, Yujin Kim 3, Hye-Ryun Kang 3, Yi Rang Na 12, Hongyoon Choi 4, Hyung-Jun Im 7 13, Yun-Sang Lee 3 4 5, Seung Hyeok Seok 1 3
1Macrophage Lab, Department of Microbiology and Immunology, and Institute of Endemic Disease, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
2Bio-MAX Institute, Seoul National University, Seoul 03080, Republic of Korea.
3Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
4Department of Nuclear Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea.
5Cancer Research Institute, Seoul National University, Seoul 03080, Republic of Korea.
6Dental Research Institute, Seoul National University, Seoul 03080, Republic of Korea.
7Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 03080, Republic of Korea.
8Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
9Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
10Department of Oral Physiology, Seoul National University, School of Dentistry, Seoul 03080, Republic of Korea.
11Research and Development Center, THERABEST, Co. Ltd., Seoul 03080, Republic of Korea.
12Transdisciplinary Department of Medicine and Advanced Technology, Seoul National University Hospital, Seoul 03080, Republic of Korea.
13Research Institute for Convergence Science, Seoul National University, Seoul 08823, Republic of Korea.