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在非人灵长类动物中使用无毒聚集诱导发光探针进行厘米级深度的近红外二区荧光成像

Centimeter-Deep NIR-II Fluorescence Imaging with Nontoxic AIE Probes in Nonhuman Primates.

作者信息

Sheng Zonghai, Li Yaxi, Hu Dehong, Min Tianliang, Gao Duyang, Ni Jen-Shyang, Zhang Pengfei, Wang Yuenan, Liu Xin, Li Kai, Zheng Hairong, Tang Ben Zhong

机构信息

Paul C. Lauterbur Research Center for Biomedical Imaging, Key Laboratory for Magnetic Resonance and Multimodality Imaging of Guangdong Province, Shenzhen Key Laboratory of Ultrasound Imaging and Therapy, CAS Key Laboratory of Health Informatics, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.

Department of Biomedical Engineering, Southern University of Science and Technology (SUSTech), Shenzhen 518055, China.

出版信息

Research (Wash D C). 2020 Sep 26;2020:4074593. doi: 10.34133/2020/4074593. eCollection 2020.

Abstract

Fluorescence probes with aggregation-induced emission (AIE) characteristics are of great importance in biomedical imaging with superior spatial and temporal resolution. However, the lack of toxicity studies and deep tissue imaging in nonhuman primates hinders their clinical translation. Here, we report the blood chemistry and histological analysis in nonhuman primates treated with AIE probes over tenfold of an intravenous dose of clinically used indocyanine green (ICG) during a study period of 36 days to demonstrate AIE probes are nontoxic. Furthermore, through bright and nontoxic AIE probes and fluorescence imaging in the second window (NIR-II, 1,000-1,700 nm), we achieve an unprecedented 1.5-centimeter-deep vascular imaging in nonhuman primates, breaking the current limitation of millimeter-deep NIR-II fluorescence imaging. Our important findings, i.e., nontoxic features of AIE probes and centimeter-deep NIR-II vascular imaging in nonhuman primates, may facilitate successful translation of AIE probes in clinical trials.

摘要

具有聚集诱导发光(AIE)特性的荧光探针在具有卓越空间和时间分辨率的生物医学成像中具有重要意义。然而,缺乏在非人类灵长类动物中的毒性研究和深层组织成像阻碍了它们的临床转化。在此,我们报告了在为期36天的研究期间,用AIE探针处理的非人类灵长类动物的血液化学和组织学分析,所用AIE探针的静脉注射剂量是临床使用的吲哚菁绿(ICG)的十倍以上,以证明AIE探针无毒。此外,通过明亮且无毒的AIE探针以及在第二窗口(近红外二区,1000 - 1700纳米)的荧光成像,我们在非人类灵长类动物中实现了前所未有的1.5厘米深度的血管成像,突破了当前毫米级深度的近红外二区荧光成像的限制。我们的重要发现,即AIE探针的无毒特性以及在非人类灵长类动物中厘米级深度的近红外二区血管成像,可能有助于AIE探针在临床试验中的成功转化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8093/7533907/518a47785754/RESEARCH2020-4074593.001.jpg

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