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.

中文翻译：

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使用工程细胞外囊泡将靶向药物递送至 ACE2+ 细胞：COVID-19 的潜在治疗方法

背景：细胞外囊泡 (EV) 正在成为抗击 COVID-19 的潜在药物载体。本研究调查了 EV 作为药物载体靶向 SARS-CoV-2 感染细胞的能力。方法：利用Xstamp技术对EV进行修饰，使其携带病毒的RBD，增强对hACE2+细胞的靶向能力，提高药物递送效率。表征证实了电动汽车适合作为药物载体。对于体外测试，A549、Caco-2 和 4T1 细胞用于评估 EVR（膜表面富集 RBD 的 EV）的靶向特异性。此外，我们利用过表达 hACE2 的离体肺组织模型作为离体模型来确认 EVR 对肺组织的靶向能力。该研究还评估了载药效率，并评估了暴露于脂多糖的 A549 肺癌细胞的抗炎活性潜力。结果：证明在膜表面成功构建了 RBD 融合 EVR。在体外和离体模型中，EVR 显着增强了其对 hACE2+ 细胞的靶向能力，使其成为安全有效的药物载体。此外，超声加载有效地将 IL-10 整合到 EVR 中，建立有效的药物递送系统，改善 LPS 刺激的 A549 细胞诱导的促炎反应。结论：这些发现表明工程化 EV 作为新型纳米药物载体具有广阔的前景，为针对 COVID-19 和其他疾病的治疗策略提供了宝贵的见解。