Cited by 218Extracellular vesicles in diseaseInhalation and Respiratory Drug DeliveryNanoparticle-Based Drug Delivery

Inhalable dry powder mRNA vaccines based on extracellular vesicles

Open access
Popowski, Kristen D., Moatti, Adele, Scull, Grant, Silkstone, Dylan, Lutz, Halle, López de Juan Abad, Blanca, George, Arianna, Belcher, Elizabeth +12 more·2022·Matter

Abstract

Respiratory diseases are a global burden, with millions of deaths attributed to pulmonary illnesses and dysfunctions. Therapeutics have been developed, but they present major limitations regarding pulmonary bioavailability and product stability. To circumvent such limitations, we developed room-temperature-stable inhalable lung-derived extracellular vesicles or exosomes (Lung-Exos) as mRNA and protein drug carriers. Compared with standard synthetic nanoparticle liposomes (Lipos), Lung-Exos exhibited superior distribution to the bronchioles and parenchyma and are deliverable to the lungs of rodents and nonhuman primates (NHPs) by dry powder inhalation. In a vaccine application, severe acute respiratory coronavirus 2 (SARS-CoV-2) spike (S) protein encoding mRNA-loaded Lung-Exos (S-Exos) elicited greater immunoglobulin G (IgG) and secretory IgA (SIgA) responses than its loaded liposome (S-Lipo) counterpart. Importantly, S-Exos remained functional at room-temperature storage for one month. Our results suggest that extracellular vesicles can serve as an inhaled mRNA drug-delivery system that is superior to synthetic liposomes.

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Crossref · 10.1016/j.matt.2022.06.012

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  • Exosomes can express surface proteins and receptors of their donor cells, allowing them to target recipient cells within the same tissue effectively.

    “One of the key benefits of exosomes is their ability to express surface proteins and receptors of their donor cells, allowing them to target recipient cells within the same tissue effectively. For example, lung spheroid cell-derived exosomes can deliver vaccines directly to lung tissue [82].”

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Authors
Popowski, K. D., Moatti, A., Scull, G., Silkstone, D., Lutz, H., López de Juan Abad, B., George, A., Belcher, E., Zhu, D., Mei, X., Cheng, X., Cislo, M., Ghodsi, A., Cai, Y., Huang, K., Li, J., Brown, A. C., Greenbaum, A., Dinh, P.-U. C., & Cheng, K.
Affiliations
  • North Carolina State University (US)
  • University of North Carolina at Chapel Hill (US)
Corresponding author
  • Dinh, Phuong-Uyen C.
  • Cheng, Ke
Venue
Matter
Publisher
Elsevier BV
Published
2022-09
Volume
5
Issue
9
Pages
2960-2974
ISSN
2590-2385 (ISSN-L)
OpenAlex
W4285008938
Cited by
218
References
50
Citations by year
2026: 33 · 2025: 62 · 2024: 59 · 2023: 55 · 2022: 8
FWCI
15.02
Type
journal article
Language
en
Open access
Locations
  • Matter (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (HL164998, HL137093, HL144002, HL149940, HL146701, HL146153, HL147357, HL123920)
  • American Heart Association (19EIA34660286, T32GM133393, 18TPA34230092)
  • College of Veterinary Medicine, North Carolina State University
  • North Carolina State University
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords
extracellular vesicles, exosomes, mRNA vaccines, dry powder inhalation, pulmonary drug delivery, liposomes, SARS-CoV-2 spike protein, secretory IgA, IgG antibody response, room-temperature stability, non-human primates

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