Inhalable exosomes outperform liposomes as mRNA and protein drug carriers to the lung
Open accessAbstract
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.
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Popowski et al. developed an inhalable vaccine utilizing lung-derived exosomes for mRNA and protein cargos; Lung-Exo exhibited pronounced mRNA translation, protein expression, and improved cargo retention in bronchioles and parenchyma, suggesting better therapeutic efficacy against SARS-CoV-2.
“They indicated that Lung-Exo exhibited pronounced mRNA translation, protein expression, and improved cargo retention in bronchioles and parenchyma, suggesting better therapeutic efficacy against severe acute respiratory syndrome coronavirus -2 (SARS-COV-2) [135].”
From Exosome for mRNA delivery: Strategies and therapeutic applications (2024) · cites this paper as [135]
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Advances in RNA-Based Therapeutics: Challenges and Innovations in RNA Delivery Systems
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Stabilized Extracellular Vesicle Formulations for Inhalable Dry Powder Development
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Extracellular Vesicles: Emergent and Multiple Sources in Wound Healing Treatment
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Pretreated exosomes by electrical stimulation accelerate bone regeneration
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Drug Delivery Systems Based on Dendritic-Cell-Derived Exosomes
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MicroRNAs won the Nobel Prize. Now, can extracellular vesicles help them become drugs?
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Minimally invasive snakebite inspired microneedle delivery system for internal organs
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Round window membrane extracellular vesicles facilitate inner ear drug delivery
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- Authors
- Popowski, K. D., López de Juan Abad, B., George, A., Silkstone, D., Belcher, E., Chung, J., Ghodsi, A., Lutz, H., Davenport, J., Flanagan, M., Piedrahita, J., Dinh, P.-U. C., & Cheng, K.
- Affiliations
- North Carolina State University (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Cheng, Ke
- ORCID
- Venue
- Extracellular Vesicle
- Publisher
- Elsevier BV
- Published
- 2022-12
- Volume
- 1
- Pages
- 100002
- ISSN
- 2773-0417 (ISSN-L)
- PMC
- PMC9213043
- OpenAlex
- W4282972187
- Cited by
- 158
- References
- 33
- Citations by year
- 2026: 28 · 2025: 51 · 2024: 50 · 2023: 19 · 2022: 10
- FWCI
- 10.61
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Extracellular Vesicle (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institutes of Health (HL149940, HL137093, HL123920, HL147357, HL146153, HL144002)
- American Heart Association Inc (18TPA34230092, 19EIA34660286)
- 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
- exosomes, pulmonary drug delivery, mRNA delivery, lipid nanoparticle vaccine, nebulization, protein drug delivery, respiratory diseases, COVID-19 vaccines
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