2. Academic Validation
  3. 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

  • J Control Release. 2014 Oct 28:192:236-42. doi: 10.1016/j.jconrel.2014.07.039.
Guo-Kai Feng 1,  Rong-Bin Liu 2,  Meng-Qing Zhang 1,  Xiao-Xuan Ye 1,  Qian Zhong 1,  Yun-Fei Xia 1,  Man-Zhi Li 1,  Jun Wang 3,  Er-Wei Song 4,  Xing Zhang 5,  Zhao-Zhong Wu 6,  Mu-Sheng Zeng 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Oncology in South China, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong, China.
  • 2 Department of Nuclear Medicine, The Second Affiliated Hospital of Guangzhou Medicine University, Guangzhou 510260, Guangdong, China.
  • 3 Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Anhui 230027, Hefei, China.
  • 4 Breast Cancer Center of Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, China.
  • 5 State Key Laboratory of Oncology in South China, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong, China. Electronic address: zhangxing@sysucc.org.cn.
  • 6 Department of Nuclear Medicine, The Second Affiliated Hospital of Guangzhou Medicine University, Guangzhou 510260, Guangdong, China. Electronic address: wu_zhaozhong@126.com.
  • 7 State Key Laboratory of Oncology in South China, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong, China. Electronic address: zengmsh@sysucc.org.cn.
PMID: 25058570 DOI: 10.1016/j.jconrel.2014.07.039
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.

Keywords

Breast Cancer; NIRF; Neuropilin-1; Phage display; SPECT; tumor targeting-peptide.

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