title: Cyanine 5.5 conjugated nanobubbles as a tumor selective contrast agent for dual ultrasound-fluorescence imaging in a mouse model.
abstract: Nanobubbles and microbubbles are non-invasive ultrasound imaging contrast agents that may potentially enhance diagnosis of tumors. However, to date, both nanobubbles and microbubbles display poor in vivo tumor-selectivity over non-targeted organs such as liver. We report here cyanine 5.5 conjugated nanobubbles (cy5.5-nanobubbles) of a biocompatible chitosan-vitamin C lipid system as a dual ultrasound-fluorescence contrast agent that achieved tumor-selective imaging in a mouse tumor model. Cy5.5-nanobubble suspension contained single bubble spheres and clusters of bubble spheres with the size ranging between 400-800 nm. In the in vivo mouse study, enhancement of ultrasound signals at tumor site was found to persist over 2 h while tumor-selective fluorescence emission was persistently observed over 24 h with intravenous injection of cy5.5-nanobubbles. In vitro cell study indicated that cy5.5-flurescence dye was able to accumulate in cancer cells due to the unique conjugated nanobubble structure. Further in vivo fluorescence study suggested that cy5.5-nanobubbles were mainly located at tumor site and in the bladder of mice. Subsequent analysis confirmed that accumulation of high fluorescence was present at the intact subcutaneous tumor site and in isolated tumor tissue but not in liver tissue post intravenous injection of cy5.5-nanobubbles. All these results led to the conclusion that cy5.5-nanobubbles with unique crosslinked chitosan-vitamin C lipid system have achieved tumor-selective imaging in vivo.
authors: Department of Nanomedicine & Biopharmaceuticals, National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors: Liyi
authors: L
authors: Mai
authors: Anna
authors: A
authors: Yao
authors: Jing
authors: J
authors: Li
authors: Qiong
authors: Q
authors: Wei
authors: Ming
authors: M
authors: Yuchi
authors: Xiaoling
authors: X
authors: He
authors: Mingyue
authors: M
authors: Ding
authors: Qibing
authors: Q
authors: Zhou
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D002232:Carbocyanines; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry; D003952:Diagnostic Imaging / Q000379:methods; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D045423:Microbubbles; D009369:Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging; D014463:Ultrasonography
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D003287:Contrast Media; C006641:ascorbyl monolaurate; D001205:Ascorbic Acid
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