Near-infrared pH-activatable fluorescent probes for imaging primary and metastatic breast tumors.
Near-infrared pH-activatable fluorescent probes for imaging primary and metastatic breast tumors.
复制标题
DOI：
10.1021/bc100584d
复制
发表时间：
2011-04-20
影响因子：
4.7
通讯作者：
Achilefu, Samuel
中科院分区：
文献类型：
--
作者：
Lee, Hyeran;Akers, Walter;Bhushan, Kumar;Bloch, Sharon;Sudlow, Gail;Tang, Rui;Achilefu, Samuel
通过将pH敏感的花青染料与靶向αvβ3整合素（ABIR）的环状精氨酸-甘氨酸-天冬氨酸（cRGD）肽缀合，开发了高度肿瘤选择性的近红外（NIR）pH可激活探针，αvβ3整合素（ABIR）是在肿瘤血管生成期间在内皮细胞中高度过表达的蛋白质。用于构建探针的NIR pH敏感染料随着pH变化表现出高光谱灵敏度。它在pH 6以上具有可忽略的荧光，但在pH 5以下变得高度荧光，pKa为4.7。这种探针是理想的成像酸性细胞器，如肿瘤溶酶体或晚期内体。细胞显微镜数据表明，cRGD探针与ABIR的结合促进了肿瘤细胞（MDA-MB- 435和4 T1/luc）中内吞介导的溶酶体蓄积和随后NIR pH可活化染料的荧光增强。在体内观察到类似的荧光增强机制，其中肿瘤在注射后4小时内明显。此外，使用该探针还在原位肿瘤小鼠模型中观察到肺转移，这通过组织学分析进一步证实。这些结果证明了使用新的整合素靶向pH敏感探针检测原发性和转移性癌症的潜力。
Highly tumor selective near-infrared (NIR) pH-activatable probe was developed by conjugating pH-sensitive cyanine dye to a cyclic Arginine-Glycine-Aspartic acid (cRGD) peptide targeting αvβ3 integrin (ABIR), a protein that is highly overexpressed in endothelial cells during tumor angiogenesis. The NIR pH-sensitive dye used to construct the probe exhibit high spectral sensitivity with pH changes. It has negligible fluorescence above pH 6 but becomes highly fluorescent below pH 5, with a pKa of 4.7. This probe is ideal for imaging acidic cell organelles such as tumor lysosomes or late endosomes. Cell microscopy data demonstrate that binding of the cRGD probe to ABIR facilitated the endocytosis-mediated lysosomal accumulation and subsequent fluorescence enhancement of the NIR pH-activatable dye in tumor cells (MDA-MB- 435 and 4T1/luc). A similar fluorescence enhancement mechanism was observed in vivo, where the tumors were evident within 4 h post injection. Moreover, lung metastases were also visualized in an orthotopic tumor mouse model using this probe, which was further confirmed by histologic analysis. These results demonstrate the potential of using the new integrin-targeted pH-sensitive probe for the detection of primary and metastatic cancer.
登录
查看更多内容
蛋白水解活性动脉粥样硬化中炎症的实时导管分子传感。
影响因子：
37.8
作者：
Jaffer FA;Vinegoni C;John MC;Aikawa E;Gold HK;Finn AV;Ntziachristos V;Libby P;Weissleder R
通讯作者：
Weissleder R
影响因子：
7.5
作者：
Kaijzel, Eric L.;van Heijningen, Paula M.;Essers, Jeroen
通讯作者：
Essers, Jeroen
影响因子：
3.6
作者：
Lee, Hyeran;Mason, J. Christian;Achilefu, Samuel
通讯作者：
Achilefu, Samuel
影响因子：
17.1
作者：
Mu, C. Jenny;LaVan, David A.;Langer, Robert S.;Zetter, Bruce R.
通讯作者：
Zetter, Bruce R.
影响因子：
--
作者：
Ogawa M;Kosaka N;Regino CA;Mitsunaga M;Choyke PL;Kobayashi H
通讯作者：
Kobayashi H