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Coupling Lipid Nanoparticle Structure and Automated Single-Particle Composition Analysis to Design Phospholipase-Responsive Nanocarriers
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Number of Authors: 92022 (English)In: Advanced Materials, ISSN 0935-9648, E-ISSN 1521-4095, Vol. 34, no 26, article id 2200839Article in journal (Refereed) Published
Abstract [en]

Lipid nanoparticles (LNPs) are versatile structures with tunable physicochemical properties that are ideally suited as a platform for vaccine delivery and RNA therapeutics. A key barrier to LNP rational design is the inability to relate composition and structure to intracellular processing and function. Here Single Particle Automated Raman Trapping Analysis (SPARTA) is combined with small-angle X-ray and neutron scattering (SAXS/SANS) techniques to link LNP composition with internal structure and morphology and to monitor dynamic LNP-phospholipase D (PLD) interactions. This analysis demonstrates that PLD, a key intracellular trafficking mediator, can access the entire LNP lipid membrane to generate stable, anionic LNPs. PLD activity on vesicles with matched amounts of enzyme substrate is an order of magnitude lower, indicating that the LNP lipid membrane structure can be used to control enzyme interactions. This represents an opportunity to design enzyme-responsive LNP solutions for stimuli-responsive delivery and diseases where PLD is dysregulated.

Place, publisher, year, edition, pages
2022. Vol. 34, no 26, article id 2200839
Keywords [en]
enzyme-responsive systems, label-free dynamic monitoring, lipid nanoparticles, phospholipase D
National Category
Chemical Sciences
Identifiers
URN: urn:nbn:se:su:diva-205216DOI: 10.1002/adma.202200839ISI: 000798835300001PubMedID: 35358374Scopus ID: 2-s2.0-85130309479OAI: oai:DiVA.org:su-205216DiVA, id: diva2:1665194
Available from: 2022-06-07 Created: 2022-06-07 Last updated: 2022-08-04Bibliographically approved

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Carroni, Marta

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