Guan Mingqiang, Wang Jian, Yang Lanbo, Zhao Zandong, Lu Kun, Zhao Liang, Xiao Jun, Li Zhihan, Shi Zhanjun
Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, PR China ; These authors contributed equally to this work.
Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, PR China.
Contemp Oncol (Pozn). 2014;18(3):165-70. doi: 10.5114/wo.2014.41384. Epub 2014 Apr 25.
Tumour endothelial cells have been proven to have molecular markers distinct from normal endothelial cells. These specific molecular markers allow for targeting of the tumour vasculature with specific pharmacological vehicles to direct diagnostic or therapeutic modalities at the endothelial cells. By performing a phage display-based screening, this study aimed to identify a certain short peptide that could specifically bind to osteosarcoma vasculature.
We performed in vivo screening in the murine models of osteosarcoma with annular Ph.D.-C7C library in the present study. To explore the in vivo binding specificity of the retrieved peptide, we conjugated the peptide with fluorescein isothiocyanate (FITC) and injected it intravenously into osteosarcoma-bearing BALB-c mice.
CTKPDKGYC was the dominant sequence isolated from in vivo screening and was named as NF-1. Fluorescence staining found that FITC-NF-1 peptide could be specifically homed to osteosarcoma vasculature while being almost undetectable in the heart, brain, lung and liver. Simultaneously, a small amount of fluorescence could also be detected in the renal glomerulus and renal tubule but not in renal vascular endothelium, indicating that FITC-NF-1 peptide might be excreted mainly through the renal-urinary route.
Our data suggest that, with high binding specificity to osteosarcoma vasculature, peptide NF-1 may have potential value in early diagnosis or targeted therapy for osteosarcoma.
肿瘤内皮细胞已被证明具有与正常内皮细胞不同的分子标记。这些特定的分子标记使得能够用特定的药物载体靶向肿瘤脉管系统，从而将诊断或治疗方式导向内皮细胞。通过基于噬菌体展示的筛选，本研究旨在鉴定一种能够特异性结合骨肉瘤脉管系统的短肽。
在本研究中，我们用环状Ph.D.-C7C文库在骨肉瘤小鼠模型中进行了体内筛选。为了探究所获得肽的体内结合特异性，我们将该肽与异硫氰酸荧光素（FITC）偶联，并将其静脉注射到荷骨肉瘤的BALB-c小鼠体内。
CTKPDKGYC是从体内筛选中分离出的优势序列，被命名为NF-1。荧光染色发现，FITC-NF-1肽能够特异性归巢到骨肉瘤脉管系统，而在心脏、脑、肺和肝脏中几乎检测不到。同时，在肾小球和肾小管中也能检测到少量荧光，但在肾血管内皮中未检测到，这表明FITC-NF-1肽可能主要通过肾泌尿途径排泄。
我们的数据表明，肽NF-1对骨肉瘤脉管系统具有高结合特异性，可能在骨肉瘤的早期诊断或靶向治疗中具有潜在价值。
