title: Molecular imaging of biological systems with a clickable dye in the broad 800- to 1,700-nm near-infrared window.
abstract: Fluorescence imaging multiplicity of biological systems is an area of intense focus, currently limited to fluorescence channels in the visible and first near-infrared (NIR-I; ∼700-900 nm) spectral regions. The development of conjugatable fluorophores with longer wavelength emission is highly desired to afford more targeting channels, reduce background autofluorescence, and achieve deeper tissue imaging depths. We have developed NIR-II (1,000-1,700 nm) molecular imaging agents with a bright NIR-II fluorophore through high-efficiency click chemistry to specific molecular antibodies. Relying on buoyant density differences during density gradient ultracentrifugation separations, highly pure NIR-II fluorophore-antibody conjugates emitting ∼1,100 nm were obtained for use as molecular-specific NIR-II probes. This facilitated 3D staining of ∼170-μm histological brain tissues sections on a home-built confocal microscope, demonstrating multicolor molecular imaging across both the NIR-I and NIR-II windows (800-1,700 nm).
authors.affiliation: Department of Chemistry, Stanford University, Stanford, CA 94305.
authors.forename: Shoujun
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Materials Science and Engineering, South University of Science and Technology of China, Shenzhen 518055, China.|Research Center for Advanced Materials and Biotechnology, Research Institute of Tsinghua University in Shenzhen, Shenzhen 518057, China.
authors.forename: Qinglai
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Chemistry, Stanford University, Stanford, CA 94305.
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Antaris
authors.affiliation: Department of Chemistry, Stanford University, Stanford, CA 94305.
authors.forename: Jingying
authors.initials: J
authors.lastname: Yue
authors.affiliation: Department of Chemistry, Stanford University, Stanford, CA 94305.
authors.forename: Zhuoran
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Materials Science and Engineering, South University of Science and Technology of China, Shenzhen 518055, China.
authors.forename: Huasen
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Materials Science and Engineering, South University of Science and Technology of China, Shenzhen 518055, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Chemistry, Stanford University, Stanford, CA 94305.|Department of Materials Science and Engineering, South University of Science and Technology of China, Shenzhen 518055, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wan
authors.affiliation: Department of Chemistry, Stanford University, Stanford, CA 94305.
authors.forename: Joy
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Stanford University, Stanford, CA 94305.
authors.forename: Shuo
authors.initials: S
authors.lastname: Diao
authors.affiliation: Department of Chemistry, Stanford University, Stanford, CA 94305.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, Stanford University, Stanford, CA 94305.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Chemistry, Stanford University, Stanford, CA 94305.
authors.forename: Yeteng
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Department of Chemistry, Stanford University, Stanford, CA 94305.
authors.forename: Kuai
authors.initials: K
authors.lastname: Yu
authors.affiliation: Department of Chemistry, Stanford University, Stanford, CA 94305.
authors.forename: Guosong
authors.initials: G
authors.lastname: Hong
authors.affiliation: Department of Neurology and Neurological Sciences, School of Medicine, Stanford University, Stanford, CA 94305.|Center for Tissue Regeneration, Repair, and Restoration, VA Palo Alto Health Care System, Palo Alto, CA 94304.
authors.forename: Jian
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Materials Science and Engineering, South University of Science and Technology of China, Shenzhen 518055, China; liangyy@sustc.edu.cn hdai@stanford.edu.
authors.forename: Yongye
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Chemistry, Stanford University, Stanford, CA 94305; liangyy@sustc.edu.cn hdai@stanford.edu.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Dai
mesh_terms: D000818:Animals; D019921:Biotinylation; D001921:Brain / Q000648:ultrastructure*; D001923:Brain Chemistry; D002294:Carcinoma, Squamous Cell / Q000648:ultrastructure; D000068818:Cetuximab / Q000032:analysis; D057930:Click Chemistry; D019085:Fluorescent Antibody Technique, Direct / Q000379:methods*; D005456:Fluorescent Dyes / Q000032:analysis*; D021621:Imaging, Three-Dimensional; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal / Q000379:methods; D015394:Molecular Structure; D043942:Nanotubes; D019906:Nuclear Magnetic Resonance, Biomolecular; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D019809:Streptavidin
chemical_list: D005456:Fluorescent Dyes; D019809:Streptavidin; D000068818:Cetuximab
keywords: NIR-II molecular imaging; NIR-II multicolor molecular imaging; bioconjugate; clickable dye; density gradient ultracentrifugation separation