Specific diagnosis of lymph node micrometastasis in breast cancer by targeting activatable near-infrared fluorescence imaging

Abstract

Axillary lymph node metastasis has always been defined as the most important prognostic factor in the treatment of early breast cancer. Ultrasound and MRI can detect only 10% of lymph node micrometastases in early breast cancer. Therefore, it is crucial to detect early breast cancer with lymph node metastasis, however, there is no current examination method for accurate diagnosis. When breast cancer presents a malignant tendency, colony stimulating factor-1 and chemokine CCL-2 absorb mononuclear cells from the surrounding environment and differentiate into M2 Tumor associated macrophages (TAM), which increase the invasion of tumor cells and further promote the development of tumors. Mannose, as a simple natural ligand, can selectively bind to TAM surface CD206 (macrophage mannose receptor, MMR). In this study, mannose was connected with near infrared dye (NIR) IR780 via disulfide bond to obtain Mannose-IR780 conjugate (MR780), which was further self-assembled into near infrared nanoprobe (MR780 NPs) with quenched fluorescence. When selectively targeting CD206 highly expressed on the surface of TAM, disulfide bond was cleaved by the glutathione enriched in the microenvironment, resulting in fluorescence recovery, thus achieving NIR fluorescence molecular imaging of TAM and diagnosis of tumor lymph node metastasis in mouse models. Our findings suggest that targeted imaging of TAM enable noninvasive and sensitive detection of metastatic lymph nodes in vivo, which is instructive for tumor therapy.