Biodistribution and Non-linear Gene Expression of mRNA LNPs Affected by Delivery Route and Particle Size
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Purpose Lipid nanoparticles (LNPs) are widely utilized as means to deliver mRNA molecules. However, metric connections between biodistribution and pharmacokinetics (PK) of the nanoparticle carrier and transgene expression dynamics remain largely unknown. Methods LNPs containing mRNAs encoding the firefly luciferase gene were prepared with varying sizes. Biodistributions of injected LNPs in mice were measured by fluorescence bioimaging or liquid chromatography with tandem mass spectrometry. In addition, luciferase expression levels were determined by bioluminescence imaging and enzyme activity assays. Results Some intramuscularly injected LNPs were found circulating in the system, resulting in accumulation in the liver and spleen, especially when the LNP sizes were relatively small. Bigger LNPs were more likely to remain at the injection site. Transgene expression in the liver was found most prominent compared with other organs and tissues. Conclusions Biomolecules such as mRNAs encapsulated in locally injected LNPs can reach other organs and tissues via systemic circulation. Gene expression levels are affected by the LNP biodistribution and pharmacokinetics (PK), which are further influenced by the particle size and injection route. As transfection efficiency varies in different organs, the LNP exposure and mRNA expression are not linearly correlated.
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LNP mRNA complexes have excellent biocompatibility and can transfect a variety of tissues and organs.
“LNP mRNA complexes have excellent biocompatibility and can transfect a variety of tissues and organs (5–9).”
From Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection (2023) · cites this paper as [9]
The Results section reports mRNA-LNP transgene expression in mouse liver, muscle, spleen, and lymph nodes, supporting transfection in multiple tissues and organs. The paper does not establish excellent biocompatibility; its Discussion instead notes potential adverse reactions from systemic exposure. (LLM, conf=0.87)
Experimental — accuracy not yet measuredIn mice, nanoparticles densely coated with PEG measuring up to 200 nm in diameter were able to spread within brain tissue, a size range achievable for LNPs.
“In mice, nanoparticles densely coated with PEG measuring up to 200 nm in diameter were able to spread within brain tissue (28), a size range achievable for LNPs (9, 29).”
From Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection (2023) · cites this paper as [9]
The Results (Physical and Biological Evaluations of Fluc-mRNA LNPs; page unavailable) report that the authors prepared LNPs in small, medium, and large size categories, supporting the point that LNP size can vary. The passages do not give diameters establishing that LNPs can reach 200 nm. Brain-tissue spread is attached to citation 28, not this source. (LLM, conf=0.76)
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Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection
Tuma, J., Chen, Y.-J., Collins, M. G., Paul, A., Li, J., Han, H., Sharma, R., Murthy, N., & Lee, H. Y. (2023) · Biochemistry · doi:10.1021/acs.biochem.3c00371 · Cited by 65 · see citing works
- Authors
- Di, J., Du, Z., Wu, K., Jin, S., Wang, X., Li, T., & Xu, Y.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Dali University (CN)
- Zhejiang University (CN)
- Purdue University West Lafayette (US)
- Corresponding author
- Li, Tonglei
- Xu, Yuhong
- Venue
- Pharmaceutical Research
- Published
- 2022-01
- Volume
- 39
- Issue
- 1
- Pages
- 105-114
- ISSN
- 0724-8741 (ISSN-L)
- 1573-904X
- PMC
- PMC8791091
- OpenAlex
- W4210268003
- Cited by
- 229
- References
- 6
- Citations by year
- 2026: 56 · 2025: 67 · 2024: 67 · 2023: 31 · 2022: 8
- FWCI
- 14.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Pharmaceutical Research (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- Zhejiang University
- 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 › Advancements in Transdermal Drug Delivery
- Keywords
- lipid nanoparticles, mRNA delivery, tissue distribution, pharmacokinetics, particle size, injection route, intramuscular injection, transgene expression, firefly luciferase, liver accumulation, systemic circulation
- MeSH terms
- Animals, Liposomes, Particle Size, RNA, Messenger, Tissue Distribution, Gene Expression, RNA, Small Interfering, Mice, Nanoparticles
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