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HACE2-Exosome-Based Nano-Bait for Concurrent SARS-CoV-2 Trapping and Antioxidant Therapy
Xiaoyi Ma1, Shiyu Guo2, Shuangrong Ruan1
1Shanghai Skin Disease Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092, P. R. China.
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.
Insights
A novel nano-bait strategy effectively inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This approach uses exosome-sheathed nanoparticles to decoy the virus and reduce inflammation, offering a promising COVID-19 treatment.
Area of Science:
- Nanotechnology
- Biomedical Engineering
- Infectious Diseases
Background:
- The COVID-19 pandemic, caused by SARS-CoV-2, poses a significant global health threat.
- SARS-CoV-2 infection triggers inflammatory and oxidative stress, leading to severe complications like pneumonia and organ failure.
- Current clinical treatments for COVID-19 require further development for safety and efficacy.
Purpose of the Study:
- To develop a novel nano-bait strategy for inhibiting SARS-CoV-2 infection.
- To simultaneously mitigate the inflammatory and oxidative microenvironment caused by the virus.
- To create a potential nanotherapeutic for COVID-19 treatment.
Main Methods:
- Engineered exosome-sheathed polydopamine (PDA@Exosome) nanoparticles displaying ACE2 receptors.
- Utilized H293T cells for exosome production and nanoparticle integration.
- Demonstrated the nano-bait's ability to bind SARS-CoV-2 S protein and neutralize radical species.
Main Results:
- The PDA@Exosome nano-bait successfully competed with host cells for S protein binding, inhibiting viral entry.
- The nanoparticles effectively intercepted and deactivated radical species, reducing oxidative stress.
- Significant attenuation of inflammatory cytokine levels was observed, mitigating organ injury.
Conclusions:
- The developed HACE2-exosome based nano-bait shows high trapping efficiency and potent antioxidant capabilities.
- This nanotherapeutic exhibits good biocompatibility, making it a promising candidate for treating COVID-19.
- The strategy offers a dual approach of viral inhibition and inflammation relief for pandemic control.
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