Abstract
Fluorescent imaging of biological systems in the second near-infrared window (NIR-II) can probe tissue at centimetre depths and achieve micrometre-scale resolution at depths of millimetres. Unfortunately, all current NIR-II fluorophores are excreted slowly and are largely retained within the reticuloendothelial system, making clinical translation nearly impossible. Here, we report a rapidly excreted NIR-II fluorophore (∼90% excreted through the kidneys within 24 h) based on a synthetic 970-Da organic molecule (CH1055). The fluorophore outperformed indocyanine green (ICG)—a clinically approved NIR-I dye—in resolving mouse lymphatic vasculature and sentinel lymphatic mapping near a tumour. High levels of uptake of PEGylated-CH1055 dye were observed in brain tumours in mice, suggesting that the dye was detected at a depth of ∼4 mm. The CH1055 dye also allowed targeted molecular imaging of tumours in vivo when conjugated with anti-EGFR Affibody. Moreover, a superior tumour-to-background signal ratio allowed precise image-guided tumour-removal surgery.
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Acknowledgements
This work was partially supported by the Office of Science (BER), US Department of Energy (DE-SC0008397) (Z.C.), NCI Cancer Center Nanotechnology Excellence Grant (CCNE-TR) U54 CA119367, the Calbrain Program, a Neurotechnology Program of California (H.D.), CA151459, the National Natural Science Foundation of China 81573383, 81373254 and 21390402, NSFHP (2014CFB704) (X.Hong), International S&T Cooperation Program of China (2015DFA30440, 2014DFB30020) (X.Hong), the National Science and Technology Major Project of the Ministry of Science and Technology of China No. 2012ZX10004801-003-011 (X.Hong), Key Project of Chinese Ministry of Education No. 313040 (X.Hong), Academic Award for Excellent PhD Candidates funded by Ministry Of Education of China (no. 5052012306001), the Fundamental Research Funds for the Central Universities (C.Q., H.C., X.Hong) and Innovation Seed Fund of Wuhan University School of Medicine (X.Hong).
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H.D., Z.C. and X.Hong conceived and designed the study, supervised the project, and wrote the manuscript. A.L.A. and H.C. designed the study, performed all the experiments, and wrote the manuscript. C.Q., B.Z. and Y.S. contributed to synthesis of the compounds. K.C., X.Z., O.K.Y., G.H., S.D. and Z.R.A. helped with optical imaging. Z.D. and X.Hu contributed to the study design and preparation of the manuscript.
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Antaris, A., Chen, H., Cheng, K. et al. A small-molecule dye for NIR-II imaging. Nature Mater 15, 235–242 (2016). https://doi.org/10.1038/nmat4476
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DOI: https://doi.org/10.1038/nmat4476
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