Department of Internal Medicine, Division of Hematology/Oncology, University of California Davis, 2921 Stockton Blvd, Sacramento, CA 95817, USA.
Department of Biomedical Engineering, University of California Davis, One Shields Avenue, Davis, CA 95616, USA.
Biomed Pharmacother. 2022 Jan;145:112469. doi: 10.1016/j.biopha.2021.112469. Epub 2021 Dec 1.
Cancer and atherosclerosis are chronic diseases that share common characteristics at both early and advanced stages and can arise from multiple factors. Both diseases are characterized by uncontrolled cell proliferation, inflammation, angiogenesis and apoptosis. Herein we investigated the ability of a peptide (CTHRSSVVC), that was previously reported to bind atherosclerotic lesions to home in the tumor microenvironment. The CTHRSSVVC peptide was synthesized on solid phase and N-terminally labeled with a sulfo-Cy5 dye. The specific binding to macrophage was evaluated in vitro with flow cytometry and immunofluorescence and in vivo for tumor targeting in BALB/c mice bearing a 4T1 tumor using optical imaging. The sulfo-Cy5-CTHRSSVVC peptide was synthesized in greater than 99% purity. No selective binding of the sulfo-Cy5-CTHRSSVVC peptide to macrophages in vitro was observed, however in vivo the sulfo-Cy5-CTHRSSVVC peptide accumulated in the 4T1 tumor, with a tumor-to-normal tissue ratio of 7.21 ± 1.44 at 2 h post injection. Ex vivo analysis of tumor tissue by confocal microscopy suggested that the sulfo-Cy5-CTHRSSVVC peptide had accumulated in the stroma of the tumor specifically, in regions of spindle shaped cells. In conclusion, although the target for the sulfo-Cy5-CTHRSSVVC peptide remains to be identified, the Cy5-CTHRSSVVC peptide warrants further investigation as a tumor imaging agent.
癌症和动脉粥样硬化是两种慢性疾病，它们在早期和晚期都有共同的特征，可以由多种因素引起。这两种疾病的特征都是细胞不受控制的增殖、炎症、血管生成和细胞凋亡。在此，我们研究了一种肽（CTHRSSVVC）的能力，该肽以前被报道可以与动脉粥样硬化病变结合，从而靶向肿瘤微环境。该 CTHRSSVVC 肽在固相上合成，并在 N 端用磺基-Cy5 染料标记。通过流式细胞术和免疫荧光法在体外评估了该肽与巨噬细胞的特异性结合，并用光学成像法在携带 4T1 肿瘤的 BALB/c 小鼠体内评估了该肽的肿瘤靶向性。合成的磺基-Cy5-CTHRSSVVC 肽纯度大于 99%。体外未观察到磺基-Cy5-CTHRSSVVC 肽对巨噬细胞的选择性结合，但体内该磺基-Cy5-CTHRSSVVC 肽在 4T1 肿瘤中积累，注射后 2 小时肿瘤与正常组织的比值为 7.21±1.44。共聚焦显微镜对肿瘤组织的离体分析表明，磺基-Cy5-CTHRSSVVC 肽特异性地在肿瘤的基质中积累，在梭形细胞区域。总之，尽管磺基-Cy5-CTHRSSVVC 肽的靶标仍有待确定，但 Cy5-CTHRSSVVC 肽作为肿瘤成像剂值得进一步研究。
