@article{27cec08e3aec4d74bd8b95277e9e8c8b,
title = "Generation of Novel Diagnostic and Therapeutic Exosomes to Detect and Deplete Protumorigenic M2 Macrophages",
abstract = "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 IgG2b 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.",
keywords = "CD206, M2 macrophages, antibody-dependent cell-mediated cytotoxicity (ADCC), breast cancer, engineered exosomes, molecular imaging",
author = "Rashid, {Mohammad Harun} and Borin, {Thaiz F.} and Roxan Ara and Ahmet Alptekin and Yutao Liu and Arbab, {Ali S.}",
note = "Funding Information: This work was supported by NIH grants no. R01CA160216, Startup fund from Georgia Cancer Center, AHA merit award 2019, and the National Institute of Neurological Disorders and Stroke Grant Numbers: 1R01NS110378, 1R21CA2293. The authors thank their former laboratory members Drs. Asm Iskander, Kartik Angara, Baghelu Achyut, and Adarsh Shankar. The authors thank Dr. Hasan Korkaya's laboratory for 4T1 cells expressing luciferase gene reporter, Dr. Satyanarayana Ande's laboratory for the Human embryonic kidney 293 cell line (HEK293), Dr. Nahid Mivechi's laboratory for the Mouse Embryonic Fibroblast cell line (MEF), Dr. Gabor Csanyi's laboratory from the vascular biology department at Augusta University for the RAW264.7 mouse macrophage cell line, and Dr. Mumtaz Rojiani and Dr. Dimitrios Moskofidis for their laboratory supply support. The authors also thank Dr. Yutao Liu's laboratory members Jingwen Cai and Hongfang Yu for the exosomes{\textquoteright} size measurements, the Histology and Electron Microscopy Core and Core Imaging Facility for Small Animals (CIFSA) from Augusta University. The authors thank their administrative personnel Tonya Fowler, Darryl Nettles, Christopher Middleton, Shelia Joyner, Denise Harper, and Quar-an Green for their support. The authors are thankful to Drs. Mark Hamrick, Hasan Korkaya, Anatolij Horuzsko, and Ahmed Chadli for their valuable suggestions. Publisher Copyright: {\textcopyright} 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim",
year = "2020",
month = jul,
day = "1",
doi = "10.1002/adtp.201900209",
language = "English (US)",
volume = "3",
journal = "Advanced Therapeutics",
issn = "2366-3987",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "7",
}