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

IF 2.2 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yao Zhang, Sheng-Jiao Song, Jin He, Zhuo-Hua Zhao, Ke Zhang, Yuan Zhang, Xing Li
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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: The 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.

利用工程细胞外囊泡向 ACE2+ 细胞靶向递送药物:COVID-19的潜在治疗方法。
背景:细胞外囊泡(EVs)正在成为抗击COVID-19的潜在药物载体。本研究探讨了EVs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 EVs 进行修饰,使其携带病毒的 RBD,从而增强了对 hACE2+ 细胞的靶向能力,提高了药物输送效率。表征证实了 EVs 作为药物载体的适用性。在体外测试中,我们使用了 A549、Caco-2 和 4T1 细胞来评估 EVRs(富含膜表面 RBD 的 EVs)的靶向特异性。此外,我们还利用过表达 hACE2 的体外肺组织模型来证实 EVRs 对肺组织的靶向能力。该研究还评估了药物负载效率,以及对暴露于脂多糖的 A549 肺癌细胞的潜在抗炎活性。结果表明,在膜表面成功构建了 RBD 融合 EVR。在体外和体内模型中,EVRs 显著增强了对 hACE2+ 细胞的靶向能力,使其成为一种安全高效的药物载体。此外,超声加载可将 IL-10 有效地结合到 EVRs 中,从而建立了一种有效的药物输送系统,可改善由 LPS 刺激的 A549 细胞诱发的促炎反应:这些研究结果表明,工程化 EVs 作为一种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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Current pharmaceutical biotechnology
Current pharmaceutical biotechnology 医学-生化与分子生物学
CiteScore
5.60
自引率
3.60%
发文量
203
审稿时长
6 months
期刊介绍: Current Pharmaceutical Biotechnology aims to cover all the latest and outstanding developments in Pharmaceutical Biotechnology. Each issue of the journal includes timely in-depth reviews, original research articles and letters written by leaders in the field, covering a range of current topics in scientific areas of Pharmaceutical Biotechnology. Invited and unsolicited review articles are welcome. The journal encourages contributions describing research at the interface of drug discovery and pharmacological applications, involving in vitro investigations and pre-clinical or clinical studies. Scientific areas within the scope of the journal include pharmaceutical chemistry, biochemistry and genetics, molecular and cellular biology, and polymer and materials sciences as they relate to pharmaceutical science and biotechnology. In addition, the journal also considers comprehensive studies and research advances pertaining food chemistry with pharmaceutical implication. Areas of interest include: DNA/protein engineering and processing Synthetic biotechnology Omics (genomics, proteomics, metabolomics and systems biology) Therapeutic biotechnology (gene therapy, peptide inhibitors, enzymes) Drug delivery and targeting Nanobiotechnology Molecular pharmaceutics and molecular pharmacology Analytical biotechnology (biosensing, advanced technology for detection of bioanalytes) Pharmacokinetics and pharmacodynamics Applied Microbiology Bioinformatics (computational biopharmaceutics and modeling) Environmental biotechnology Regenerative medicine (stem cells, tissue engineering and biomaterials) Translational immunology (cell therapies, antibody engineering, xenotransplantation) Industrial bioprocesses for drug production and development Biosafety Biotech ethics Special Issues devoted to crucial topics, providing the latest comprehensive information on cutting-edge areas of research and technological advances, are welcome. Current Pharmaceutical Biotechnology is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments.
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