Rashid Mohammad Harun, Borin Thaiz F, Ara Roxan, Alptekin Ahmet, Liu Yutao, Arbab Ali S
Laboratory of Tumor Angiogenesis, Georgia Cancer Center, Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA 30912, USA.
Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Adv Ther (Weinh). 2020 Jul;3(7). doi: 10.1002/adtp.201900209. Epub 2020 May 4.
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, In-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.
鉴于其促肿瘤功能以及在大多数生存率较低的恶性肿瘤中的普遍存在；早期检测和干预CD206阳性M2巨噬细胞可能会改善临床结果。为了确定M2巨噬细胞的体内分布，采用了基于In-奥昔碘的靶向外泌体放射性标记。当将这些放射性标记的靶向外泌体注射到荷乳腺肿瘤小鼠体内时，外泌体聚集在原发性肿瘤的周边、肺、脾和肝中的转移灶处。放射性的体外定量也显示出类似的分布。将DiI染料标记的外泌体注射到同一小鼠体内，在体外荧光显微镜成像中显示外泌体与CD206阳性M2巨噬细胞粘附。此外，这些工程化外泌体被用于携带IgG2b的Fc部分，以增强抗体依赖性细胞介导的细胞毒性。结果表明，靶向M2巨噬细胞的治疗性外泌体在体外和体内均可消耗M2巨噬细胞，并减轻肿瘤负担，提高转移性乳腺癌模型的生存率。
