Real-time in vivo molecular detection of primary tumors and metastases with ratiometric activatable cell-penetrating peptides.
Real-time in vivo molecular detection of primary tumors and metastases with ratiometric activatable cell-penetrating peptides.
复制标题
DOI：
10.1158/0008-5472.can-12-2969
复制
发表时间：
2013-01-15
期刊：
影响因子：
11.2
通讯作者：
Nguyen QT
中科院分区：
文献类型：
--
作者：
Savariar EN;Felsen CN;Nashi N;Jiang T;Ellies LG;Steinbach P;Tsien RY;Nguyen QT
转移性疾病的管理是癌症治疗不可或缺的一部分。对转移的评估通常需要手术切除所有解剖易感的淋巴结以进行体外病理检查。我们报道了一类新的比率激活的细胞穿透肽，它们以Cy5为远红外荧光供体，Cy7为近红外荧光受体。Cy5被抑制，以利于Cy7重排，直到中间连接物被肿瘤相关的基质金属蛋白酶-2和9(MMP2，9)或弹性酶切割。这种切割使Cy5：Cy7发射比增加40倍，并触发含有Cy5的片段的组织滞留。这一比率增加提供了一种快速和可量化的指标，以提高敏感性和特异性来识别原发肿瘤以及肝和淋巴结的转移。这项技术比现有的非比率蛋白水解酶传感器和前哨淋巴结检测方法有了显著的进步，这些方法没有提供关于癌症侵袭的信息。
Management of metastatic disease is integral to cancer treatment. Evaluation of metastases often requires surgical removal of all anatomically susceptible lymph nodes for ex vivo pathologic examination. We report a family of novel ratiometric activatable cell-penetrating peptides, which contain Cy5 as far red fluorescent donor and Cy7 as near-infrared fluorescent acceptor. Cy5 is quenched in favor of Cy7 reemission until the intervening linker is cut by tumor-associated matrix metalloproteinases-2 and 9 (MMP2,9) or elastases. Such cleavage increases the Cy5:Cy7 emission ratio 40-fold and triggers tissue retention of the Cy5-containing fragment. This ratiometric increase provides an accelerated and quantifiable metric to identify primary tumors and metastases to liver and lymph nodes with increased sensitivity and specificity. This technique represents a significant advance over existing nonratiometric protease sensors and sentinel lymph node detection methods, which give no information about cancer invasion.