An antigen-strengthened dye-modified fully-human-nanobody-based immunoprobe for second near infrared bioimaging of metastatic tumors

Yibing Shi; Huifang Wu; Weiqiang Hu; Yujia Jin; Mengya Kong; Yulu Wang; Binfan Chen; Quanxiao Li; Keke Huang; Zhenlin Yang; Fuyou Li; Yanling Wu; Tianlei Ying

doi:10.1016/j.biomaterials.2022.121637

An antigen-strengthened dye-modified fully-human-nanobody-based immunoprobe for second near infrared bioimaging of metastatic tumors

Biomaterials. 2022 Aug:287:121637. doi: 10.1016/j.biomaterials.2022.121637. Epub 2022 Jun 15.

Authors

Yibing Shi¹, Huifang Wu¹, Weiqiang Hu², Yujia Jin¹, Mengya Kong³, Yulu Wang¹, Binfan Chen¹, Quanxiao Li¹, Keke Huang¹, Zhenlin Yang⁴, Fuyou Li⁵, Yanling Wu⁶, Tianlei Ying⁷

Affiliations

¹ MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
² Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Shanghai, 200032, China.
³ Department of Chemistry, Fudan University, Shanghai, 200433, China.
⁴ Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
⁵ Department of Chemistry, Fudan University, Shanghai, 200433, China. Electronic address: fyli@fudan.edu.cn.
⁶ MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China. Electronic address: yanlingwu@fudan.edu.cn.
⁷ MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China. Electronic address: tlying@fudan.edu.cn.

PMID: 35728407
DOI: 10.1016/j.biomaterials.2022.121637

Abstract

Conventional immunoprobes have absorption capabilities across the visible to near infrared (NIR-I, 650-900 nm) region. Recently, second near infrared (NIR-II, 1000-1700 nm) window have gained much attention due to their deeper penetration depth and improved visualization. Here, we describe the design and synthesis of a fully human nanobody-based fluorescent immunoprobe (ICGM-n501) for NIR-II bioimaging with strengthened fluorescent emission by antigen for the first time. By site-directed conjugation of an FDA-approved dye analogue, indocyanine green decorated with maleimide (ICGM), into a tumor-specific n501, ICGM-n501 provides real-time monitoring of abdominal transportation pathway of antibody-based bioagents with high resolution (0.21 mm), presents better accuracy and lower dosage (0.21 μmol kg^-1) in bioimaging of peritoneal metastatic tumors than bioluminescence agent D-luciferin. In this work, ICGM-n501 demonstrates its potential in clinical surgery guidance, provide an expanded category of available NIR-II fluorophores and a template for next-generation immunoassay bioagents.

Keywords: Bioimaging; Dye; Fully human nanobody; Immunoprobe; Metastatic tumor; Second near infrared.