SPECT and Near-Infrared Fluorescence Imaging of Breast Cancer with a Neuropilin-1-Targeting Peptide
SPECT and Near-Infrared Fluorescence Imaging of Breast Cancer with a Neuropilin-1-Targeting Peptide
复制标题
使用 Neuropilin-1 靶向肽对乳腺癌进行 SPECT 和近红外荧光成像
DOI：
10.1016/j.jconrel.2014.07.039
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发表时间：
2014-10-28
影响因子：
10.8
通讯作者：
Zeng, Mu-Sheng
中科院分区：
文献类型：
--
作者：
Feng, Guo-Kai;Liu, Rong-Bin;Zeng, Mu-Sheng
乳腺癌是最常见的恶性肿瘤，也是女性癌症死亡的主要原因。分子影像学是一种很有前途的方法，用于乳腺癌的早期检测和分期以及评估治疗反应。肿瘤靶向肽是分子成像的有效靶向载体。在这里，我们确定了一个乳腺癌靶向肽CLKADKAKC（CK 3）含有一个隐藏的C-末端规则基序，可能介导其结合神经纤毛蛋白-1（NRP-1），一个有吸引力的治疗靶点，其表达与乳腺癌患者的不良预后相关。噬菌体CK 3与NRP-1阳性乳腺癌细胞结合，这可以通过肽CK 3以剂量依赖性方式或通过敲低NRP-1表达来抑制。一致地，NRP-1在细胞中的过表达增加了噬菌体CK 3的结合。此外，肽CK 3与NRP-1共定位。重要的是，与先前报道的具有暴露的C-末端规则基序的NRP-1靶向肽不同，肽CK 3在体内不渗透到肺和心脏中，这可以使其更具临床应用性。单光子发射CT（SPECT）和近红外荧光（NIRF）成像显示肽CK 3在裸鼠异种移植瘤中富集。结论：CK 3肽作为一种新型的NRP-1靶向肽，可用于乳腺癌的分子影像学研究，为乳腺癌的诊断、分期和疗效评价提供了新的途径。(C)2014爱思唯尔有限公司版权所有。
Breast cancer is the most common malignant cancer and is the leading cause of cancer death among females. Molecular imaging is a promising approach for the early detection and staging of breast cancer as well as for assessing therapeutic responses. Tumor-targeting peptides are effective targeting vehicles for molecular imaging. Here, we identified a breast cancer-targeting peptide CLKADKAKC (CK3) contains a cryptic C-end rule motif that may mediate its binding to neuropilin-1 (NRP-1), an attractive therapeutic target which expression was associated with poor outcome of the patients with breast cancer. Phage CK3 bound to NRP-1-positive breast cancer cells, which could be inhibited by peptide CK3 in a dose-dependent manner or by knock-down NRP-1 expression. Consistently, NRP-1 overexpression in cells increased the binding of phage CK3. Furthermore, peptide CK3 co-localized with NRP-1. Importantly, unlike previously reported NRP-1-targeting peptides with exposed C-end rule motifs, peptide CK3 did not penetrate into lungs and heart in vivo, which could make it more clinically applicable. Single-photon emission CT (SPECT) and near-infrared fluorescence (NIRF) imaging showed enrichment of peptide CK3 to the xenograft tumors in nude mice. In conclusion, as a novel NRP-1-targeting peptide, peptide CK3 could be used for breast cancer molecular imaging, which may represent a new avenue for breast cancer diagnostics, staging and assessments of therapeutic response. (C) 2014 Elsevier B.V. All rights reserved.