title: A near-infrared fluorescent heptamethine indocyanine dye with preferential tumor accumulation for in vivo imaging.
abstract: Near-infrared (NIR) fluorescence imaging holds great promise for tumor imaging due to low tissue autofluorescence and deep tissue penetration. However, most tumor-targeting fluorescent probes require combination of targeting agents and fluorescent reporters. In this study, we described a NIR heptamethine cyanine dye, IR-780 iodide, with preferential accumulation in multiple tumor cells without the necessity of chemical conjugation. The IR-780 iodide was found to retain in tumors but not normal cells in multiple tumor xenografts in nude mice and chemically-induced lung tumors in C57BL/6 mice. The fluorescent signal of tumors could persist at least 20 days with a significant signal-to-background ratio. As a lipophilic cation, a predominant accumulation of IR-780 iodide was shown in the mitochondria of tumor cells owing to the high magnitude of mitochondrial membrane potential in tumor cells than normal cells. We further showed that the transportation of IR-780 iodide into tumor cells was mediated by the organic anion transporter peptides (OATPs) because the dye accumulation was significantly inhibited by sulfobromophthalein (BSP), a competitive inhibitor of OATPs. Our study shows that IR-780 iodide that preferentially accumulates in tumor cells and is natively NIR fluorescent would be useful in tumor detection.
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, College of Preventive Medicine, Third Military Medical University, Chongqing Engineering Research Center for Nanomedicine, Chongqing 400038, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Yongping
authors.initials: Y
authors.lastname: Su
authors.forename: Shenglin
authors.initials: S
authors.lastname: Luo
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
authors.forename: Xu
authors.initials: X
authors.lastname: Tan
authors.forename: Song
authors.initials: S
authors.lastname: Fan
authors.forename: Lilong
authors.initials: L
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhou
authors.forename: Tianmin
authors.initials: T
authors.lastname: Cheng
authors.forename: Chunmeng
authors.initials: C
authors.lastname: Shi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D007211:Indoles / Q000737:chemistry; D008175:Lung Neoplasms / Q000175:diagnosis; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000175:diagnosis*; D019265:Spectroscopy, Near-Infrared / Q000379:methods*
chemical_list: C548458:2-(2-(2-chloro-3-((1,3-dihydro-3,3-dimethyl-1-propyl-2H-indol-2-ylidene)ethylidene)-1-cyclohexen-1-yl)ethenyl)-3,3-dimethyl-1-propylindolium; D005456:Fluorescent Dyes; D007211:Indoles