Near-infrared-labeled peptide multimer functions as phage mimic for high affinity, specific targeting of colonic adenomas in vivo (with videos).
Near-infrared-labeled peptide multimer functions as phage mimic for high affinity, specific targeting of colonic adenomas in vivo (with videos).
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DOI：
10.1016/j.gie.2012.07.017
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发表时间：
2012-12
影响因子：
7.7
通讯作者：
Wang TD
中科院分区：
文献类型：
--
作者：
Joshi BP;Liu Z;Elahi SF;Appelman HD;Wang TD
荧光标记的肽正在开发中，以改善结肠发育不良的内镜检测。证明一种近红外肽多聚体作为噬菌体模拟物用于结肠腺瘤的体内检测。使用三赖氨酸作为树枝状楔形物合成肽多聚体以模拟肽在噬菌体上的呈递，并且所有肽（包括多聚体）用Cy5.5荧光标记。小动物成像设施基因工程CPC;自发发展结肠腺瘤的Apc小鼠。将NIR标记的AKPGYLS肽多聚体局部施用到小鼠的远端结肠中，并捕获腺瘤的内窥镜图像。荧光强度通过靶-背景（T/B）比率定量，成像后用卡尺测量腺瘤尺寸。使用共聚焦显微镜和流式细胞术对冷冻切片标本和细胞进行特异性肽结合的验证。结肠腺瘤和邻近正常粘膜的荧光T/B比值。AKP-多聚体、单体、三赖氨酸核心和Cy5.5导致平均T/B比分别为3.85±0.25、2.21±0.13、1.56±0.12和1.19±0.11，在体内成像上p<0.01。与其他探针相比，肽多聚体显示出更高的对比度和更高的特异性。在流式细胞术和荧光显微镜下，肽多聚体与单体和三赖氨酸核心相比，与HT 29细胞的结合显著更强。测定多聚体的结合亲和力为6.4 nM/L，时间常数为0.1136 min-1（8.8 min）。仅对远端结肠腺瘤进行成像。肽多聚体联合收割机结合多个单独肽的强度以增强结合相互作用，并显示出对肿瘤靶标的显著更高的特异性和亲和力。
Fluorescent-labeled peptides are being developed to improve the endoscopic detection of colonic dysplasia. To demonstrate a near-infrared peptide multimer that functions as a phage mimic for in vivo detection of colonic adenomas. A peptide multimer was synthesized using trilysine as a dendritic wedge to mimic the presentation of peptides on phage and all peptides, including the multimer, were fluorescent-labeled with Cy5.5. Small animal imaging facility Genetically engineered CPC;Apc mouse that spontaneously develop colonic adenomas. NIR-labeled AKPGYLS peptide multimer was administered topically into distal colon of mice, and endoscopic images of adenomas were captured. Fluorescence intensities were quantified by target-to-background (T/B) ratios, and adenoma dimensions were measured with calipers after imaging. Validation of specific peptide binding was performed on cryosectioned specimens and cells using confocal microscopy and flow cytometry. Fluorescence T/B ratios from colonic adenomas and adjacent normal-appearing mucosa. AKP-multimer, monomer, trilysine core and Cy5.5 resulted in mean T/B ratios of 3.85±0.25, 2.21±0.13, 1.56±0.12, and 1.19±0.11, respectively, p<0.01 on in vivo imaging. Peptide multimer showed higher contrast and greater specificity for dysplastic crypts as compared to other probes. Peptide multimer demonstrated significantly greater binding to HT29 cells on flow cytometry and fluorescence microscopy in comparison to monomer and trilysine core. A binding affinity of 6.4 nM/Land time constant of 0.1136 min−1 (8.8 min) was measured for multimer. Only distal colonic adenomas were imaged. Peptide multimers combine strengths of multiple individual peptides to enhance binding interactions and demonstrate significantly higher specificity and affinity for tumor targets.
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影响因子：
29.4
作者：
Li M;Anastassiades CP;Joshi B;Komarck CM;Piraka C;Elmunzer BJ;Turgeon DK;Johnson TD;Appelman H;Beer DG;Wang TD
通讯作者：
Wang TD
影响因子：
12.6
作者：
Lakoff, Josh;Paszat, Lawrence F.;Rabeneck, Linda
通讯作者：
Rabeneck, Linda
影响因子：
9.3
作者：
Heresbach, D.;Barrioz, T.;Ponchan, T.
通讯作者：
Ponchan, T.
影响因子：
4.7
作者：
Liu S
通讯作者：
Liu S
影响因子：
9.7
作者：
Oyama, T;Sykes, KF;Brown, KC
通讯作者：
Brown, KC