Generation of Novel Diagnostic and Therapeutic Exosomes to Detect and Deplete Protumorigenic M2 Macrophages.

Given their protumorigenic function and prevalence in most malignant tumors with lower survival; early detection, and intervention of CD206-positive M2 macrophages may boost the clinical outcome. To determine in vivo distribution of M2 macrophages, 111In-oxine-based radiolabeling of the targeted exosomes is adopted. When these radiolabeled targeted exosomes are injected into breast tumor-bearing mice, exosomes accumulate at the periphery of the primary tumor, metastatic foci in the lungs, spleen, and liver. Ex vivo quantification of radioactivity also shows similar distribution. Injecting DiI dye-labeled exosomes into the same mice shows adherence of exosomes to the CD206-positive M2 macrophages on ex vivo fluorescent microscopy imaging. In addition, these engineered exosomes are utilized to carry the Fc portion of lgG2b with the intention of augmenting antibody-dependent cell-mediated cytotoxicity. It is demonstrated that M2 macrophage targeting therapeutic exosomes deplete M2 macrophages both in vitro and in vivo, and reduce tumor burden, increasing survival in a metastatic breast cancer model.