Cited by 188RNA Interference and Gene DeliveryNanoparticle-Based Drug DeliveryAdvancements in Transdermal Drug Delivery

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Multiparametric approach for the evaluation of lipid nanoparticles for siRNA delivery

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Alabi, Christopher A., Love, Kevin T., Sahay, Gaurav, Yin, Hao, Luly, Kathryn M., Langer, Robert, Anderson, Daniel G.·2013·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1306529110PMC PMC3740846

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Abstract

Nanoparticle-mediated siRNA delivery is a complex process that requires transport across numerous extracellular and intracellular barriers. As such, the development of nanoparticles for efficient delivery would benefit from an understanding of how parameters associated with these barriers relate to the physicochemical properties of nanoparticles. Here, we use a multiparametric approach for the evaluation of lipid nanoparticles (LNPs) to identify relationships between structure, biological function, and biological activity. Our results indicate that evaluation of multiple parameters associated with barriers to delivery such as siRNA entrapment, pK a , LNP stability, and cell uptake as a collective may serve as a useful prescreening tool for the advancement of LNPs in vivo. This multiparametric approach complements the use of in vitro efficacy results alone for prescreening and improves in vitro–in vivo translation by minimizing false negatives. For the LNPs used in this work, the evaluation of multiple parameters enabled the identification of LNP pK a as one of the key determinants of LNP function and activity both in vitro and in vivo. It is anticipated that this type of analysis can aid in the identification of meaningful structure–function–activity relationships, improve the in vitro screening process of nanoparticles before in vivo use, and facilitate the future design of potent nanocarriers.

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Authors: Alabi, C. A., Love, K. T., Sahay, G., Yin, H., Luly, K. M., Langer, R., & Anderson, D. G.
Affiliations: Koch Institute for Integrative Cancer Research At MIT (US)
University of Rochester (US)
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142;
Harvard–MIT Division of Health Sciences and Technology (US)
ORCID: Alabi, Christopher A.
Sahay, Gaurav
Yin, Hao
Luly, Kathryn M.
Anderson, Daniel G.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2013-07-23
Volume: 110
Issue: 32
Pages: 12881-12886
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.1306529110
PMC: PMC3740846
OpenAlex: W2155534998
Cited by: 188
References: 39
Citations by year: 2026: 15 · 2025: 17 · 2024: 26 · 2023: 9 · 2022: 13 · 2021: 18 · 2020: 11 · 2019: 11 · 2018: 9 · 2017: 8 · 2016: 17 · 2015: 16 · 2014: 15 · 2013: 3
FWCI: 7.62
Type: journal article
Language: en
Open access: green
europepmc.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
Funders: National Institutes of Health (4r37eb000244-34)
National Cancer Institute (P30CA014051)
National Institute of Biomedical Imaging and Bioengineering (R37-EB000244)
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, siRNA delivery, cellular uptake, in vitro to in vivo translation, nanocarrier design
MeSH terms: Animals, Factor VII, Flow Cytometry, HeLa Cells, Hemolysis, Humans, Lipids, Luciferases, Mice, Inbred C57BL, Reproducibility of Results, Gene Transfer Techniques, Microscopy, Confocal, Fluorescence Resonance Energy Transfer, RNA Interference, RNA, Small Interfering, Mice, Nanoparticles

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Multiparametric approach for the evaluation of lipid nanoparticles for siRNA delivery

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