Targeted Imaging of Tumor Associated Macrophages in Breast Cancer

Abstract

Breast cancer is a highly heterogeneous disease lacking prognostic markers. Tumor-associated macrophages (TAMs) in the tumor microenvironment are associated with distant metastasis as well as poorer outcomes in breast cancer. Therefore, monitoring TAMs may guide prognostic assessment. This study explores an imaging modality based on a two-step click chemistry procedure for detecting TAMs in breast cancer. Mannose-targeted liposomes (MAN-lipo-AAG) and non-targeted liposomes (lipo-AAG) encapsulating Ac4GalNAz were prepared and comprehensively characterized. The sizes of the prepared MAN-lipo-AAG and lipo-AAG were 126 ± 0.22 and 93 ± 0.23 nm, respectively. In vitro studies demonstrated higher uptake of MAN-lipo-AAG than lipo-AAG by RAW264.7 cells. Moreover, flow cytometry and confocal microscopy confirmed that bright, homogeneous fluorescence labeling was present on RAW264.7 cell membranes in the MAN-lipo-AAG group. Furthermore, in vivo analysis indicated that MAN-lipo-AAG, compared with lipo-AAG, had higher accumulation in a 4T1 xenograft model and higher uptake by mannose-overexpressing TAMs. This study describes a promising approach for specific and non-invasive TAM-targeted imaging via metabolic glycoengineering.

Keywords

• breast cancer
• cd206
• click chemistry
• tumor associated macrophages