Department of Biomedical Engineering, School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Lane, Gulou District, Nanjing, 210009, China.
Contrast Media Mol Imaging. 2014 Mar-Apr;9(2):122-34. doi: 10.1002/cmmi.1545.
Bombesin (BBN), an analog of gastrin-releasing peptide (GRP), of which the receptors are over-expressed on various tumor cells, is able to bind to GRP receptor specifically. In this study, a near-infrared fluorescent dye (MPA) and polyethylene glycol (PEG) were conjugated to BBN analog to form BBN[7-14]-MPA and BBN[7-14]-SA-PEG-MPA. The successful synthesis of the two probes was proved by the characterization via sodium dodecylsulfate-polyacrylamide gel electrophoresis, infrared and optical spectra. Cellular uptakes studies indicated that BBN-based probes were mediated by gastrin-releasing peptide receptors (GRPR) on tumor cells and the PEG modified probe had higher affinity. The dynamic distribution and clearance investigations showed that the BBN-based probes were eliminated by the liver-kidney pathway. Furthermore, both of the BBN-based probes displayed tumor-targeting ability in GRPR over-expressed tumor-bearing mice. The PEG modified probe exhibited faster and higher tumor targeting capability than BBN[7-14]-MPA. The results implied that BBN[7-14]-SA-PEG-MPA could act as an effective fluorescence probe for tumor imaging.
蛙皮素（Bombesin，BBN）是胃泌素释放肽（gastrin-releasing peptide，GRP）的类似物，其受体在各种肿瘤细胞上过度表达，能够特异性结合 GRP 受体。在这项研究中，我们将近红外荧光染料（MPA）和聚乙二醇（PEG）与 BBN 类似物偶联，形成 BBN[7-14]-MPA 和 BBN[7-14]-SA-PEG-MPA。通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳、红外和光谱分析对这两种探针进行了表征，证明了它们的成功合成。细胞摄取研究表明，基于 BBN 的探针是通过肿瘤细胞上的胃泌素释放肽受体（GRPR）介导的，而经过 PEG 修饰的探针具有更高的亲和力。动态分布和清除研究表明，基于 BBN 的探针通过肝肾途径清除。此外，这两种基于 BBN 的探针在过表达 GRPR 的荷瘤小鼠中均显示出肿瘤靶向能力。经过 PEG 修饰的探针比 BBN[7-14]-MPA 具有更快、更高的肿瘤靶向能力。这些结果表明，BBN[7-14]-SA-PEG-MPA 可以作为一种有效的荧光探针用于肿瘤成像。
