Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.
Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, China Medical University, Shenyang, China.
Mol Oncol. 2023 May;17(5):872-886. doi: 10.1002/1878-0261.13352. Epub 2022 Dec 30.
Annexin A2 (ANXA2) encodes an oncoprotein whose expression has been found to correlate with poorer overall survival (OS) of pancreatic adenocarcinoma (PAAD) patients. Although peptides are available for targeting ANXA2, none of these were initially selected to target this protein specifically. Here, we took ANXA2 as a molecular target for PAAD and employed the phage display technique to screen for a new ANXA2-targeted peptide. The resultant heptapeptide, YW7, was firstly labeled with fluorescein isothiocyanate (FITC) to evaluate its selectivity in cellular uptake, and further with the near-infrared fluorescent (NIRF) dye Cy7 to assess in vivo distribution in a mouse model bearing PANC-1 human pancreatic cancer xenografic tumors. We found that both FITC-YW7 and Cy7-YW7 probes showed significantly higher uptake in PANC-1 cells compared to the HPDE6-C7 pancreatic epithelium cells. Mice intravenously injected with Cy7-YW7 showed higher tumor-to-background ratios (TBRs) (~ 2.7-fold) in tumor tissues compared to those injected with Cy7 alone. Our study suggested that YW7 is a novel peptide targeting ANXA2 and Cy7-YW7 is an NIRF probe potentially useful for the early detection of PAAD.
膜联蛋白 A2(ANXA2)编码一种癌蛋白,其表达与胰腺导管腺癌(PAAD)患者的总生存率(OS)较差相关。虽然有针对 ANXA2 的肽可供使用,但最初没有一种肽被专门选择来靶向这种蛋白质。在这里,我们将 ANXA2 作为 PAAD 的分子靶标,并采用噬菌体展示技术筛选新的针对 ANXA2 的肽。所得的七肽 YW7 首先用异硫氰酸荧光素(FITC)标记,以评估其在细胞摄取中的选择性,并用近红外荧光(NIRF)染料 Cy7 进一步评估其在携带 PANC-1 人胰腺癌细胞异种移植瘤的小鼠模型中的体内分布。我们发现,与 HPDE6-C7 胰腺上皮细胞相比,FITC-YW7 和 Cy7-YW7 探针在 PANC-1 细胞中的摄取明显更高。与单独注射 Cy7 相比,静脉注射 Cy7-YW7 的小鼠在肿瘤组织中的肿瘤与背景比(TBR)(~2.7 倍)更高。我们的研究表明,YW7 是一种针对 ANXA2 的新型肽,Cy7-YW7 是一种潜在用于早期检测 PAAD 的 NIRF 探针。