Precision Targeting of Tumor Macrophages with a CD206 Binding Peptide.

Abstract

Tumor-associated macrophages (TAMs) expressing the multi-ligand endocytic receptor mannose receptor (CD206/MRC1) contribute to tumor immunosuppression, angiogenesis, metastasis, and relapse. Here, we describe a peptide that selectively targets MRC1-expressing TAMs (MEMs). We performed in vivo peptide phage display screens in mice bearing 4T1 metastatic breast tumors to identify peptides that target peritoneal macrophages. Deep sequencing of the peptide-encoding inserts in the selected phage pool revealed enrichment of the peptide CSPGAKVRC (codenamed "UNO"). Intravenously injected FAM-labeled UNO (FAM-UNO) homed to tumor and sentinel lymph node MEMs in different cancer models: 4T1 and MCF-7 breast carcinoma, B16F10 melanoma, WT-GBM glioma and MKN45-P gastric carcinoma. Fluorescence anisotropy assay showed that FAM-UNO interacts with recombinant CD206 when subjected to reducing conditions. Interestingly, the GSPGAK motif is present in all CD206-binding collagens. FAM-UNO was able to transport drug-loaded nanoparticles into MEMs, whereas particles without the peptide were not taken up by MEMs. In ex vivo organ imaging, FAM-UNO showed significantly higher accumulation in sentinel lymph nodes than a control peptide. This study suggests applications for UNO peptide in diagnostic imaging and therapeutic targeting of MEMs in solid tumors.

• Authors: Pablo Scodeller, Lorena Simón-Gracia, Sergei Kopanchuk, Allan Tobi, Kalle Kilk, Pille Säälik, Kaarel Kurm, Mario Leonardo Squadrito, Venkata Ramana Kotamraju, Ago Rinken, Michele De Palma, Erkki Ruoslahti, Tambet Teesalu
• Journal: Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 14655 (11 07 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 29116108 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Lectins, C-Type
• Mannose Receptor
• Mannose-Binding Lectins
• Peptides
• Receptors, Cell Surface
• Recombinant Proteins

Topics

• Animals
• Drug Delivery Systems (methods)
• Female
• Lectins, C-Type (metabolism)
• Macrophages (drug effects)
• Mammary Neoplasms, Experimental (drug therapy)
• Mannose Receptor
• Mannose-Binding Lectins (metabolism)
• Mice
• Mice, Inbred BALB C
• Neoplasm Transplantation
• Peptides (therapeutic use)
• Receptors, Cell Surface (metabolism)
• Recombinant Proteins