Repurposing an atherosclerosis targeting peptide for tumor imaging

• Published in: Biomedicine & pharmacotherapy Vol. 145; p. 112469
• Main Authors: Kovacs, Luciana, Davis, Ryan A., Ganguly, Tanushree, Chammas, Roger, Sutcliffe, Julie L.
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.01.2022; Elsevier
• Subjects: Animals; Antigens, CD - analysis; Antigens, Differentiation, Myelomonocytic - analysis; Atherosclerosis; Carbocyanines - pharmacology; Disease Models, Animal; Fluorescent Antibody Technique; Fluorescent Dyes - pharmacology; Humans; Immunohistochemistry; Macrophages - immunology; Mice; Neoplasms - diagnostic imaging; Optical imaging; Optical Imaging - methods; Peptide; Peptides - chemical synthesis; Peptides - chemistry; Peptides - metabolism; Peptides - pharmacology; Plaque, Atherosclerotic - diagnostic imaging; Protein Binding; Receptors, Cell Surface - analysis; Receptors, Scavenger - analysis; Stroma; Sulfo-Cy5; THP-1 Cells; Tumor; OCT; DMSO; MRI; SPPS; LPS; TFA; α-SMA; DBU; Atherosclerosis; Tumor; Fmoc; HATU; DMF; Peptide; Cy5; TIPS; IFNγ; PMA; DIPEA; IL-4; Stroma; Optical imaging; IL-13; ACN; TNBS; ROI; IL-10; MeOH; PET; Sulfo-Cy5
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2021.112469

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. •Optimization of synthesis of the sulfo-Cy5-CTHRSSVVC-CONH2 peptide.•The CTHRSSVVC peptide was repurposed as a candidate for tumor imaging.•The sulfo-Cy5-CTHRSSVVC-CONH2 peptide does not bind macrophages.•The sulfo-Cy5-CTHRSSVVC-CONH2 peptide targeted spindle-shaped cells in tumor stroma.