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Improved Tumor Targeting and Longer Retention Time of NIR Fluorescent Probes Using Bioorthogonal Chemistry
Zhang, Xianghan1; Wang, Bo1; Zhao, Na1; Tian, Zuhong3; Dai, Yunpeng1; Nie, Yongzhan3; Tian, Jie1,2; Wang, Zhongliang1; Chen, Xiaoyuan4
2017
发表期刊THERANOSTICS
卷号7期号:15页码:3794-3802
文章类型Article
摘要The traditional labeling method for targeted NIR fluorescence probes requires directly covalent-bonded conjugation of targeting domains and fluorophores in vitro. Although this strategy works well, it is not sufficient for detecting or treating cancers in vivo, due to steric hindrance effects that relatively large fluorophore molecules exert on the configurations and physiological functions of specific targeting domains. The copper-free, "click-chemistry"-assisted assembly of small molecules in living systems may enhance tumor accumulation of fluorescence probes by improving the binding affinities of the targeting factors. Here, we employed a vascular homing peptide, GEBP11, as a targeting factor for gastric tumors, and we demonstrate its effectiveness for in vivo imaging via click-chemistry-mediated conjugation with fluorescence molecules in tumor xenograft mouse models. This strategy showed higher binding affinities than those of the traditional conjugation method, and our results showed that the tumor accumulation of click-chemistry-mediated probes are 11-fold higher than that of directly labeled probes. The tracking life was prolonged by 12-fold, and uptake of the probes into the kidney was reduced by 6.5-fold. For lesion tumors of different sizes, click-chemistry-mediated probes can achieve sufficient signal-to-background ratios (3.5-5) for in vivo detection, and with diagnostic sensitivity approximately 3.5 times that of traditional labeling probes. The click-chemistry-assisted detection strategy utilizes the advantages of "small molecule" probes while not perturbing their physiological functions; this enables tumor detection with high sensitivity and specific selectivity.
关键词Click Chemistry Nir Fluorescence Probes Gebp11 Gastric Cancer
WOS标题词Science & Technology ; Life Sciences & Biomedicine
DOI10.7150/thno.20912
关键词[WOS]GUIDED CANCER-SURGERY ; GASTRIC-CANCER ; VIVO ; PEPTIDE ; BINDING ; MICE
收录类别SCI
语种英语
项目资助者Program of the National Basic Research and Development Program of China (973)(2013CB733803) ; National Natural Science Foundation of China(81227901 ; national 1000 Young Talents Program of China ; 81402467 ; 81671753)
WOS研究方向Research & Experimental Medicine
WOS类目Medicine, Research & Experimental
WOS记录号WOS:000408444200014
引用统计
文献类型期刊论文
条目标识符http://ir.ia.ac.cn/handle/173211/20723
专题中国科学院分子影像重点实验室
作者单位1.Xidian Univ, Engn Res Ctr Mol Imaging & Neuroimaging, Minist Educ, Sch Life Sci & Technol, Xian 710026, Shaanxi, Peoples R China
2.Chinese Acad Sci, Inst Automat, Beijing 100190, Peoples R China
3.Fourth Mil Med Univ, Inst Digest Dis, Xijing Hosp, Xian 710032, Shaanxi, Peoples R China
4.Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA
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Zhang, Xianghan,Wang, Bo,Zhao, Na,et al. Improved Tumor Targeting and Longer Retention Time of NIR Fluorescent Probes Using Bioorthogonal Chemistry[J]. THERANOSTICS,2017,7(15):3794-3802.
APA Zhang, Xianghan.,Wang, Bo.,Zhao, Na.,Tian, Zuhong.,Dai, Yunpeng.,...&Chen, Xiaoyuan.(2017).Improved Tumor Targeting and Longer Retention Time of NIR Fluorescent Probes Using Bioorthogonal Chemistry.THERANOSTICS,7(15),3794-3802.
MLA Zhang, Xianghan,et al."Improved Tumor Targeting and Longer Retention Time of NIR Fluorescent Probes Using Bioorthogonal Chemistry".THERANOSTICS 7.15(2017):3794-3802.
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