In Vitro and in Vivo mRNA Delivery Using Lipid-Enveloped pH-Responsive Polymer Nanoparticles
Open accessAbstract
Biodegradable core--shell structured nanoparticles with a poly(β-amino ester) (PBAE) core enveloped by a phospholipid bilayer shell were developed for in vivo mRNA delivery with a view toward delivery of mRNA-based vaccines. The pH-responsive PBAE component was chosen to promote endosome disruption, while the lipid surface layer was selected to minimize toxicity of the polycation core. Messenger RNA was efficiently adsorbed via electrostatic interactions onto the surface of these net positively charged nanoparticles. In vitro, mRNA-loaded particle uptake by dendritic cells led to mRNA delivery into the cytosol with low cytotoxicity, followed by translation of the encoded protein in these difficult-to-transfect cells at a frequency of ~30%. Particles loaded with mRNA administered intranasally (i.n.) in mice led to the expression of the reporter protein luciferase in vivo as soon as 6 h after administration, a time point when naked mRNA given i.n. showed no expression. At later time points, luciferase expression was detected in naked mRNA-treated mice, but this group showed a wide variation in levels of transfection, compared to particle-treated mice. This system may thus be promising for noninvasive delivery of mRNA-based vaccines.
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pH-responsive polymers, such as poly(β-amino ester), can be incorporated into lipid nanoparticles to facilitate endosomal escape of mRNA molecules.
“For example, pH-responsive polymers, such as poly (β-amino ester), can be incorporated into lipid nanoparticles to facilitate endosomal escape of mRNA molecules160.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [160]
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- Authors
- Su, X., Fricke, J., Kavanagh, D. G., & Irvine, D. J.
- Affiliations
- Department of Materials Science and Engineering
- Ragon Institute of MGH, MIT and Harvard (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Irvine, Darrell J.
- Venue
- Molecular Pharmaceutics
- Publisher
- American Chemical Society (ACS)
- Published
- 2011-04-01
- Volume
- 8
- Issue
- 3
- Pages
- 774-787
- ISSN
- 1543-8384 (ISSN-L)
- 1543-8392
- PMC
- PMC3354687
- OpenAlex
- W1585872414
- Cited by
- 287
- References
- 91
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 24 · 2023: 21 · 2022: 32 · 2021: 19 · 2020: 21 · 2019: 17 · 2018: 23 · 2017: 19 · 2016: 15 · 2015: 20 · 2014: 14 · 2013: 14 · 2012: 13
- FWCI
- 5.59
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- PubMed Central
- Funders
- Howard Hughes Medical Institute
- National Institute of Allergy and Infectious Diseases (R21AI083133, AI83133, P30AI060354)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- mRNA delivery, poly(β-amino ester), pH-responsive nanoparticles, core-shell nanoparticles, mRNA vaccines, dendritic cells, intranasal drug delivery, electrostatic adsorption, luciferase expression, biodegradable nanoparticles
- MeSH terms
- Animals, Cell Line, Drug Carriers, Hydrogen-Ion Concentration, Lipids, Mice, Inbred BALB C, Polymers, RNA, Messenger, Mice, Nanoparticles
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