HACE2-Exosome-Based Nano-Bait for Concurrent SARS-CoV-2 Trapping and Antioxidant Therapy
Xiaoyi Ma, Shiyu Guo, Shuangrong Ruan, Yao Liu, Jie Zang, Yushan Yang, Haiqing Dong, Yan Li, Yan Li, Tianbin Ren, Mao‐Mao An, Yongyong Li, Yongyong Li
Abstract
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.