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Generation of novel diagnostic and therapeutic exosomes to detect and deplete pro-tumorigenic M2-macrophages

Given their pro-tumorigenic 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, we adopted 111In-oxine-based radiolabeling of the targeted exosomes. When injected these radiolabeled targeted exosomes into breast tumor-bearing mice, exosomes accumulated at the periphery of the primary tumor, metastatic foci in the lungs, spleen, and liver. Ex vivo quantification of radioactivity also showed similar distribution. Injected DiI dye-labeled exosomes into the same mice showed adherence of exosomes to the CD206-positive M2-macrophages on ex vivo fluorescent microscopy imaging. In addition, we utilized these engineered exosomes to carry the Fc portion of IgG2b with the intention of augmenting antibody-dependent cell-mediated cytotoxicity. We have auspiciously 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.