SPECT and near-infrared fluorescence imaging of breast cancer with a neuropilin-1-targeting peptide.

Abstract

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.

• Authors: Guo-Kai Feng, Rong-Bin Liu, Meng-Qing Zhang, Xiao-Xuan Ye, Qian Zhong, Yun-Fei Xia, Man-Zhi Li, Jun Wang, Er-Wei Song, Xing Zhang, Zhao-Zhong Wu, Mu-Sheng Zeng
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 192 Pg. 236-42 (Oct 28 2014) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 25058570 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Peptides
• Neuropilin-1

Topics

• Amino Acid Sequence
• Animals
• Breast (metabolism, pathology)
• Breast Neoplasms (diagnosis, metabolism)
• Cell Line, Tumor
• Female
• Humans
• Mice
• Mice, Nude
• Molecular Imaging (methods)
• Molecular Sequence Data
• Neuropilin-1 (analysis, metabolism)
• Optical Imaging (methods)
• Peptides (chemistry, metabolism)
• Tomography, Emission-Computed, Single-Photon (methods)