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Sci Rep. 2017 Nov 7;7(1):14655. doi: 10.1038/s41598-017-14709-x.

Precision Targeting of Tumor Macrophages with a CD206 Binding Peptide.

Author information

1
Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 14B, Tartu, 50411, Estonia. pablo.david.scodeller@ut.ee.
2
Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 N, Torrey Pines Road, La Jolla, 92097, California, USA. pablo.david.scodeller@ut.ee.
3
Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 14B, Tartu, 50411, Estonia.
4
Institute of Chemistry, University of Tartu, Ravila 14, Tartu, 50411, Estonia.
5
Department of Biochemistry, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 14B, Tartu, 50411, Estonia.
6
School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Swiss Federal Institute of Technology, Lausanne, CH-1015, Lausanne, Switzerland.
7
Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 N, Torrey Pines Road, La Jolla, 92097, California, USA.
8
Center for Nanomedicine and Department of Cell, Molecular and Developmental Biology, University of California, Santa Barbara Santa Barbara, 93106, California, USA.
9
Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 14B, Tartu, 50411, Estonia. tambet.teesalu@ut.ee.
10
Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 N, Torrey Pines Road, La Jolla, 92097, California, USA. tambet.teesalu@ut.ee.
11
Center for Nanomedicine and Department of Cell, Molecular and Developmental Biology, University of California, Santa Barbara Santa Barbara, 93106, California, USA. tambet.teesalu@ut.ee.

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.

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