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Rational synthesis of IR820-albumin complex for NIR-II fluorescence imaging-guided surgical treatment of tumors and gastrointestinal obstruction.

ABSTRACT: IR820, an analog of FDA-approved indocyanine green, is a promising second near-infrared window (NIR-II) fluorescence probe with better NIR-II fluorescence stability and great clinical transformation potential. Moreover, its fluorescence can be further remarkably enhanced by the interaction with albumin. Therefore, it is significant to flexibly design IR820-albumin complex using endogenous or exogenetic albumin to meet the requirements of different biological applications. Herein, we show the rational synthesis of IR820-albumin complex for NIR-II fluorescence imaging-guided surgical treatment of tumors and gastrointestinal obstruction. We compared the NIR-II fluorescence imaging ability of IR820 pre-incubated with albumin or not to visualize tumors and the gastrointestinal tract in vivo and found that the formation of IR820-albumin was essential for the intense NIR-II fluorescence. For imaging-guided tumor treatment, after intravenous injection of free IR820, IR820-albumin complex can be formed in vivo due to the presence of plenty of albumin in the blood. For imaging-guided gastrointestinal obstruction removal, IR820-albumin complex should be synthesized in vitro before oral administration. NIR-II fluorescence imaging-guided surgeries were successfully realized in both tumor resection and gastrointestinal obstruction removal. Besides, toxicity assessments in vitro and in vivo confirmed the good biocompatibility of IR820. Our study provides a flexible paradigm for IR820-based NIR-II fluorescence imaging and surgical navigation towards different diseases.

SUBMITTER: Feng X

PROVIDER: S-EPMC9023119 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Rational synthesis of IR820-albumin complex for NIR-II fluorescence imaging-guided surgical treatment of tumors and gastrointestinal obstruction.

Feng Xinyu X Cao Yuan Y Zhuang Pengrui P Cheng Ran R Zhang Xuejun X Liu Hong H Wang Guohe G Sun Shao-Kai SK

RSC advances 20220421 19

IR820, an analog of FDA-approved indocyanine green, is a promising second near-infrared window (NIR-II) fluorescence probe with better NIR-II fluorescence stability and great clinical transformation potential. Moreover, its fluorescence can be further remarkably enhanced by the interaction with albumin. Therefore, it is significant to flexibly design IR820-albumin complex using endogenous or exogenetic albumin to meet the requirements of different biological applications. Herein, we show the rat ...[more]

PMID: 35481109

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Project description:BackgroundSurgery is the cornerstone of colorectal cancer (CRC) treatment, yet complete removal of the tumour remains a challenge. The second near-infrared window (NIR-II, 1000-1700 nm) fluorescent molecular imaging is a novel technique, which has broad application prospects in tumour surgical navigation. We aimed to evaluate the ability of CEACAM5-targeted probe for CRC recognition and the value of NIR-II imaging-guided CRC resection.MethodsWe constructed the probe 2D5-IRDye800CW by conjugated anti-CEACAM5 nanobody (2D5) with near-infrared fluorescent dye IRDye800CW. The performance and benefits of 2D5-IRDye800CW at NIR-II were confirmed by imaging experiments in mouse vascular and capillary phantom. Then mouse colorectal cancer subcutaneous tumour model (n = 15), orthotopic model (n = 15), and peritoneal metastasis model (n = 10) were constructed to investigate biodistribution of probe and imaging differences between NIR-I and NIR-II in vivo, and then tumour resection was guided by NIR-II fluorescence. Fresh human colorectal cancer specimens were incubated with 2D5-IRDye800CW to verify its specific targeting ability.Findings2D5-IRDye800CW had an NIR-II fluorescence signal extending to 1600 nm and bound specifically to CEACAM5 with an affinity of 2.29 nM. In vivo imaging, 2D5-IRDye800CW accumulated rapidly in tumour (15 min) and could specifically identify orthotopic colorectal cancer and peritoneal metastases. All tumours were resected under NIR-II fluorescence guidance, even smaller than 2 mm tumours were detected, and NIR-II had a higher tumour-to-background ratio than NIR-I (2.55 ± 0.38, 1.94 ± 0.20, respectively). 2D5-IRDye800CW could precisely identify CEACAM5-positive human colorectal cancer tissue.Interpretation2D5-IRDye800CW combined with NIR-II fluorescence has translational potential as an aid to improve R0 surgery of colorectal cancer.FundingsThis study was supported by Beijing Natural Science Foundation (JQ19027), the National Key Research and Development Program of China (2017YFA0205200), National Natural Science Foundation of China (NSFC) (61971442, 62027901, 81930053, 92059207, 81227901, 82102236), Beijing Natural Science Foundation (L222054), CAS Youth Interdisciplinary Team (JCTD-2021-08), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16021200), the Zhuhai High-level Health Personnel Team Project (Zhuhai HLHPTP201703), the Fundamental Research Funds for the Central Universities (JKF-YG-22-B005) and Capital Clinical Characteristic Application Research (Z181100001718178). The authors would like to acknowledge the instrumental and technical support of the multi-modal biomedical imaging experimental platform, Institute of Automation, Chinese Academy of Sciences.

Dataset Information

Rational synthesis of IR820-albumin complex for NIR-II fluorescence imaging-guided surgical treatment of tumors and gastrointestinal obstruction.

Publications

Rational synthesis of IR820-albumin complex for NIR-II fluorescence imaging-guided surgical treatment of tumors and gastrointestinal obstruction.

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