In Situ Deployment of Engineered Extracellular Vesicles Into the Tumor Niche Via myeloid-derived Suppressor Cells


Posted: 2021-10-18 19:00:00
Adv Healthc Mater . 2021 Oct 18;e2101619. doi: 10.1002/adhm.202101619. Online ahead of print. Silvia Duarte-Sanmiguel 1 , Ana Panic 1 , Daniel Dodd 1 2 , Ana Salazar-Puerta 1 , Jordan T Moore 1 , William R Lawrence 2 , Kylie Nairon 1 , Carlie Francis 1 , Natalie Zachariah 1 , Billy McCoy 1 , Rithvik Turaga 1 , Aleksander Skardal 1 , William E Carson 3 , Natalia Higuita-Castro 1 3 4 , Daniel Gallego-Perez 1 3 Affiliations Expand Affiliations 1 Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA. 2 Biomedical Sciences Graduate Program, The Ohio State University, Columbus, OH, 43210, USA. 3 Department of Surgery, The Ohio State University, Columbus, OH, 43210, USA. 4 Biophysics Program, The Ohio State University, Columbus, OH, 43210, USA. Item in Clipboard Silvia Duarte-Sanmiguel et al. Adv Healthc Mater. 2021. Show details Display options Display options Format Adv Healthc Mater . 2021 Oct 18;e2101619. doi: 10.1002/adhm.202101619. Online ahead of print. Authors Silvia Duarte-Sanmiguel 1 , Ana Panic 1 , Daniel Dodd 1 2 , Ana Salazar-Puerta 1 , Jordan T Moore 1 , William R Lawrence 2 , Kylie Nairon 1 , Carlie Francis 1 , Natalie Zachariah 1 , Billy McCoy 1 , Rithvik Turaga 1 , Aleksander Skardal 1 , William E Carson 3 , Natalia Higuita-Castro 1 3 4 , Daniel Gallego-Perez 1 3 Affiliations 1 Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA. 2 Biomedical Sciences Graduate Program, The Ohio State University, Columbus, OH, 43210, USA. 3 Department of Surgery, The Ohio State University, Columbus, OH, 43210, USA. 4 Biophysics Program, The Ohio State University, Columbus, OH, 43210, USA. Item in Clipboard CiteDisplay options Display options Format Abstract Extracellular vesicles (EVs) have emerged as a promising carrier system for the delivery of therapeutic payloads in multiple disease models, including cancer. However, effective targeting of EVs to cancerous tissue remains a challenge. Here, we show that non-viral transfection of myeloid-derived suppressor cells (MDSCs) can be leveraged to drive targeted release of engineered EVs that can modulate transfer and overexpression of therapeutic anti-cancer genes in tumor cells and tissue. MDSCs are immature immune cells that exhibit enhanced tropism toward tumor tissue and play a role in modulating tumor progression. Current MDSC research has been mostly focused on mitigating immunosuppression in the tumor niche; however, the tumor homing abilities of these cells present untapped potential to deliver EV therapeutics directly to cancerous tissue. In vivo and ex vivo studies with murine models of breast cancer showed that non-viral transfection of MDSCs does not hinder their ability to home to cancerous tissue. Moreover, transfected MDSCs can release engineered EVs and mediate anti-tumoral responses via paracrine signaling, including decreased invasion/metastatic activity and increased apoptosis/necrosis. Altogether, these findings indicate that MDSCs could be a powerful tool for the deployment of EV-based therapeutics to tumor tissue. This article is protected by copyright. All rights reserved. Keywords: extracellular vesicles; myeloid-derived suppressor cells; non-viral gene and cell therapies; solid tumors; tumor tropism. This article is protected by copyright. All rights reserved. [x] Cite Copy Format: Send To [x]

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