Targeted Drug Delivery to ACE2+ Cells Using Engineered Extracellular Vesicles: A Potential Therapeutic Approach for COVID-19

Title:Targeted Drug Delivery to ACE2+ Cells Using Engineered Extracellular Vesicles: A Potential Therapeutic Approach for COVID-19

Volume: 25

Author(s): Yao Zhang, Sheng-Jiao Song, Jin He, Zhuo-Hua Zhao, Ke Zhang, Yuan Zhang and Xing Li*

Affiliation:

• National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry (Shaanxi Normal University), The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, 710119, China

Keywords: Extracellular vesicles, Drug-targeted delivery, SARS-CoV-2, hACE2.

Abstract: Background: Extracellular vesicles (EVs) are emerging as potential drug carriers in the fight against COVID-19. This study investigates the ability of EVs as drug carriers to target SARS-CoV-2-infected cells.

Methods: EVs were modified using Xstamp technology to carry the virus’s RBD, enhancing targeting ability to hACE2+ cells and improving drug delivery efficiency. Characterization confirmed EVs’ suitability as drug carriers. For in vitro tests, A549, Caco-2, and 4T1 cells were used to assess the targeting specificity of EVRs (EVs with membrane-surface enriched RBD). Moreover, we utilized an ex vivo lung tissue model overexpressing hACE2 as an ex vivo model to confirm the targeting capability of EVRs toward lung tissue. The study also evaluated drug loading efficiency and assessed the potential of the anti-inflammatory activity on A549 lung cancer cells exposed to lipopolysaccharide.

Results demonstrate the successful construction of RBD-fused EVRs on the membrane-surface. In both in vitro and ex vivo models, EVRs significantly enhance their targeting ability towards hACE2+ cells, rendering them a safe and efficient drug carrier. Furthermore, ultrasound loading efficiently incorporates IL-10 into EVRs, establishing an effective drug delivery system that ameliorates the pro-inflammatory response induced by LPS-stimulated A549 cells.

Conclusion: These findings indicate promising opportunities for engineered EVs as a novel nanomedicine carrier, offering valuable insights for therapeutic strategies against COVID-19 and other diseases.

Cite this article as:

Zhang Yao, Song Sheng-Jiao, He Jin, Zhao Zhuo-Hua, Zhang Ke, Zhang Yuan and Li Xing*, Targeted Drug Delivery to ACE2+ Cells Using Engineered Extracellular Vesicles: A Potential Therapeutic Approach for COVID-19, Current Pharmaceutical Biotechnology 2024; 25 () . https://dx.doi.org/10.2174/0113892010282251240324123038