Single-Particle Spectroscopic Chromatography Reveals Heterogeneous RNA Loading and Size Correlations in Lipid Nanoparticles Article Swipe
Sixuan Li
,
Yizong Hu
,
Jinghan Lin
,
Zachary Schneiderman
,
Fangchi Shao
,
Lai Wei
,
Andrew Li
,
Kuangwen Hsieh
,
Efrosini Kokkoli
,
Tine Curk
,
Hai‐Quan Mao
,
Tza‐Huei Wang
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1021/acsnano.4c02341
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1021/acsnano.4c02341
Lipid nanoparticles (LNP) have emerged as pivotal delivery vehicles for RNA therapeutics. Previous research and development usually assumed that LNPs are homogeneous in population, loading density, and composition. Such perspectives are difficult to examine due to the lack of suitable tools to characterize these physicochemical properties at the single-nanoparticle level. Here, we report an integrated spectroscopy-chromatography approach as a generalizable strategy to dissect the complexities of multicomponent LNP assembly. Our platform couples cylindrical illumination confocal spectroscopy (CICS) with single-nanoparticle free solution hydrodynamic separation (SN-FSHS) to simultaneously profile population identity, hydrodynamic size, RNA loading levels, and distributions of helper lipid and PEGylated lipid of LNPs at the single-particle level and in a high-throughput manner. Using a benchmark siRNA LNP formulation, we demonstrate the capability of this platform by distinguishing seven distinct LNP populations, quantitatively characterizing size distribution and RNA loading level in wide ranges, and more importantly, resolving composition-size correlations. This SN-FSHS-CICS analysis provides critical insights into a substantial degree of heterogeneity in the packing density of RNA in LNPs and size-dependent loading-size correlations, explained by kinetics-driven assembly mechanisms of RNA LNPs.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1021/acsnano.4c02341
- https://pubs.acs.org/doi/pdf/10.1021/acsnano.4c02341
- OA Status
- bronze
- Cited By
- 14
- References
- 61
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4399370143
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Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4399370143Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1021/acsnano.4c02341Digital Object Identifier
- Title
-
Single-Particle Spectroscopic Chromatography Reveals Heterogeneous RNA Loading and Size Correlations in Lipid NanoparticlesWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-06-05Full publication date if available
- Authors
-
Sixuan Li, Yizong Hu, Jinghan Lin, Zachary Schneiderman, Fangchi Shao, Lai Wei, Andrew Li, Kuangwen Hsieh, Efrosini Kokkoli, Tine Curk, Hai‐Quan Mao, Tza‐Huei WangList of authors in order
- Landing page
-
https://doi.org/10.1021/acsnano.4c02341Publisher landing page
- PDF URL
-
https://pubs.acs.org/doi/pdf/10.1021/acsnano.4c02341Direct link to full text PDF
- Open access
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YesWhether a free full text is available
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-
bronzeOpen access status per OpenAlex
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https://pubs.acs.org/doi/pdf/10.1021/acsnano.4c02341Direct OA link when available
- Concepts
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Particle size, Nanoparticle, Materials science, Particle (ecology), RNA, Nanotechnology, Chemical physics, Chemical engineering, Chromatography, Chemistry, Physical chemistry, Biochemistry, Biology, Ecology, Engineering, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
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14Total citation count in OpenAlex
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2025: 10, 2024: 4Per-year citation counts (last 5 years)
- References (count)
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61Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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