HACE2-Exosome-Based Nano-Bait for Concurrent SARS-CoV‑2 Trapping and Antioxidant Therapy

• Published in: ACS applied materials & interfaces Vol. 14; no. 4; pp. 4882 - 4891
• Main Authors: Ma, Xiaoyi, Guo, Shiyu, Ruan, Shuangrong, Liu, Yao, Zang, Jie, Yang, Yushan, Dong, Haiqing, Li, Yan, Ren, Tianbin, An, Maomao, Li, Yongyong
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 02.02.2022
• Subjects: Antioxidants - pharmacology; Antiviral Agents - pharmacology; Biological and Medical Applications of Materials and Interfaces; COVID-19 - drug therapy; COVID-19 - genetics; COVID-19 - pathology; COVID-19 - virology; Cytokines - genetics; Epithelial Cells - drug effects; Epithelial Cells - virology; Exosomes - drug effects; Exosomes - genetics; Humans; Pandemics; SARS-CoV-2 - drug effects; SARS-CoV-2 - pathogenicity; Virus Internalization - drug effects; COVID-19; SARS-CoV-2; nano-bait; polydopamine; cytokine release syndrome; exosome
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.1c19541

Corona Virus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is seriously threatening human health. Following SARS-CoV-2 infection, immune cell infiltration creates an inflammatory and oxidative microenvironment, which can cause pneumonia, severe acute respiratory syndrome, kidney failure, and even death. Clinically, a safe and effective treatment strategy remains to be established. Herein, a nano-bait strategy for inhibition of SARS-CoV-2 infection by redirecting viral attack while simultaneously relieving inflammation is developed. Specifically, the nano-bait was based on the exosome-sheathed polydopamine (PDA@Exosome) nanoparticles, which were generated by exocytosis of the PDA nanoparticles from H293T cells. In this approach, PDA@Exosome inherits from the source cells of H293T cells a surface display of ACE2 through pre-engineered expression. The resulting PDA@Exosome can compete with ACE2-expressing epithelial cells for S protein binding, in either the pre-exposure or post-exposure route. Moreover, relying on the ability of PDA to intercept and deactivate radical species, the PDA@Exosome can significantly attenuate the level of inflammatory cytokines by mediating oxidative stress, a major cause of organ injury. Due to its high trapping, multiple antioxidant ability, and good biocompatibility, the HACE2-exosome based nano-bait is a promising robust antiviral nanotherapeutics for the ongoing COVID-19 pandemic.