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

2020.05.04.

Rashid, M. H. et al., Advanced Therapeutics, 2020

Introduction

We would like to introduce Professor Ali Arbab and his colleagues’ work in this blog. Professor Ali Arbab is the leader of the Tumor Angiogenesis Initiative, and director of the Core Imaging Facilities for Small Animals (CIFSA) in Augusta, GA. His research group interests are antiangiogenic therapy and vascular mimicry in glioblastoma (GBM) and breast cancer, targeting the tumor microenvironment of GBM and breast cancers as a better option to counter therapy resistance. Recently they have explored engineered exosomes as imaging and therapeutic probes to target immune-suppressive cells in tumor microenvironment. Professor Ali Arbab has 30 years of experience in imaging science involving MRI, SPECT, CT, ultrasound, and optical imaging modalities. The core facility provides MRI and optical imaging resources, and they also have a nanoScan SPECT/CT from Mediso.

Summary

Exosomes have emerged as potential tools for a drug delivery system that can target specific tissues or cells. M2 macrophages participate in immune suppression, epithelial to mesenchymal transition, invasion, angiogenesis, tumor progression, and subsequent metastasis foci formation. In their recent work they determined in vivo distribution of M2 macrophages with 111In-oxine-based radiolabeling of the targeted exosomes. The research 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.

Mediso's nanoScan SPECT/CT was used to detect the biodistribution of 111In-oxine-labeled exosomes targeting CD206-positive M2 macrophages.

Figure 4.d from the publication, After 3 h of intravenous injection showed significant accumulation of M2-targeting exosome in tumor, lung, spleen, lymph node, and bones. 111In-oxine-labeled non-targeting exosomes (HEK293 exo) and CD206-positive M2 macrophage targeting exosomes (M2-targeting exo) were injected into the 4T1 tumor bearing mice. One group was treated with Clophosome to deplete macrophages. Yellow and green arrows denote lymph node and bone metastasis, respectively.

Publication: https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.201900209

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