Inhalable exosomes outperform liposomes as mRNA and protein drug carriers to the lung.
Inhalable exosomes outperform liposomes as mRNA and protein drug carriers to the lung.
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DOI：
10.1016/j.vesic.2022.100002
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发表时间：
2022-12
期刊：
影响因子：
--
通讯作者：
Cheng, Ke
中科院分区：
文献类型：
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作者：
Popowski, Kristen D;Lopez de Juan Abad, Blanca;George, Arianna;Silkstone, Dylan;Belcher, Elizabeth;Chung, Jaewook;Ghodsi, Asma;Lutz, Halle;Davenport, Jada;Flanagan, Mallory;Piedrahita, Jorge;Dinh, Phuong-Uyen C;Cheng, Ke
呼吸道疾病是全球发病率和死亡率的主要原因之一，再加上正在进行的2019年冠状病毒病(新冠肺炎)大流行。虽然已经开发出了mRNA脂质纳米粒(LNP)疫苗，但它们的肌肉递送限制了肺部的生物利用度。吸入纳米颗粒疗法提供了局部药物输送，最大限度地减少了目标不良反应，并具有更好的患者依从性。然而，LNP平台需要大量重新配制吸入性给药。肺源性胞外囊泡提供了一种生物纳米颗粒替代品，这种生物纳米颗粒天然地优化了信使核糖核酸的翻译和输送到肺细胞。我们比较了商业标准生物细胞外囊泡(HEK-Exo)和LNPs(Lipo)在肺组织中的生物分布，在雾化给药后，肺-Exo显示出更好的mRNA和蛋白质在细支气管和实质中的分布和滞留。这表明，吸入性肺-Exo可提供具有增强肺部生物利用度和治疗效果的信使核糖核酸和蛋白质药物。
Respiratory diseases are among the leading causes of morbidity and mortality worldwide, coupled with the ongoing coronavirus disease 2019 (COVID-19) pandemic. mRNA lipid nanoparticle (LNP) vaccines have been developed, but their intramuscular delivery limits pulmonary bioavailability. Inhalation of nanoparticle therapeutics offers localized drug delivery that minimizes off targeted adverse effects and has greater patient compliance. However, LNP platforms require extensive reformulation for inhaled delivery. Lung-derived extracellular vesicles (Lung-Exo) offer a biological nanoparticle alternative that is naturally optimized for mRNA translation and delivery to pulmonary cells. We compared the biodistribution of Lung-Exo against commercially standard biological extracellular vesicles (HEK-Exo) and LNPs (Lipo), where Lung-Exo exhibited superior mRNA and protein cargo distribution to and retention in the bronchioles and parenchyma following nebulization administration. This suggests that inhaled Lung-Exo can deliver mRNA and protein drugs with enhanced pulmonary bioavailability and therapeutic efficacy.