Natural Killer Cell‐Derived Extracellular Vesicles as Potential Anti‐Viral Nanomaterials

Siyoung A Lim; Nathan Ho; Sophia Chen; Eun Ji Chung

doi:10.1002/adhm.202304186

Natural Killer Cell‐Derived Extracellular Vesicles as Potential Anti‐Viral Nanomaterials

Adv Healthc Mater. 2024 Apr 27:e2304186. doi: 10.1002/adhm.202304186. Online ahead of print.

[Article in Catalan]

Authors

Siyoung A Lim¹, Nathan Ho¹, Sophia Chen¹, Eun Ji Chung^{1

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Affiliations

¹ Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, 90089, USA.
² Department of Medicine, Division of Nephrology and Hypertension, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90089, USA.
³ Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA, 90089, USA.
⁴ Department of Surgery, Division of Vascular Surgery and Endovascular Therapy, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90089, USA.
⁵ Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA, 90089, USA.
⁶ Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90089, USA.
⁷ Bridge Institute, University of Southern California, Los Angeles, CA, 90089, USA.
⁸ Michelson Center for Convergent Bioscience, 1002 Childs Way, MCB 377, Los Angeles, CA, 90089, USA.

PMID: 38676697
DOI: 10.1002/adhm.202304186

Abstract

In viral infections, natural killer (NK) cells exhibit anti-viral activity by inducing apoptosis in infected host cells and impeding viral replication through heightened cytokine release. Extracellular vesicles derived from NK cells (NK-EVs) also contain the membrane composition, homing capabilities, and cargo that enable anti-viral activity. These characteristics, and their biocompatibility and low immunogenicity, give NK-EVs the potential to be a viable therapeutic platform. This study characterizes the size, EV-specific protein expression, cell internalization, biocompatibility, and anti-viral miRNA cargo to evaluate the anti-viral properties of NK-EVs. After 48 h of NK-EV incubation in inflamed A549 lung epithelial cells, or conditions that mimic lung viral infections such as during COVID-19, cells treated with NK-EVs exhibit upregulated anti-viral miRNA cargo (miR-27a, miR-27b, miR-369-3p, miR-491-5p) compared to the non-treated controls and cells treated with control EVs derived from lung epithelial cells. Additionally, NK-EVs effectively reduce expression of viral RNA and pro-inflammatory cytokine (TNF-α, IL-8) levels in SARS-CoV-2 infected Vero E6 kidney epithelial cells and in infected mice without causing tissue damage while significantly decreasing pro-inflammatory cytokine compared to non-treated controls. Herein, this work elucidates the potential of NK-EVs as safe, anti-viral nanomaterials, offering a promising alternative to conventional NK cell and anti-viral therapies.

Keywords: COVID‐19; SARS‐CoV‐2; anti‐viral; extracellular vesicles; nanoparticles; natural killer cells.

Publication types

English Abstract

Grants and funding

EAGERDMR2132744/National Science Foundation