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Coupling Lipid Nanoparticle Structure and Automated Single-Particle Composition Analysis to Design Phospholipase-Responsive Nanocarriers
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Rekke forfattare: 92022 (engelsk)Inngår i: Advanced Materials, ISSN 0935-9648, E-ISSN 1521-4095, Vol. 34, nr 26, artikkel-id 2200839Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
2022. Vol. 34, nr 26, artikkel-id 2200839
Emneord [en]
enzyme-responsive systems, label-free dynamic monitoring, lipid nanoparticles, phospholipase D
HSV kategori
Identifikatorer
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
Tilgjengelig fra: 2022-06-07 Laget: 2022-06-07 Sist oppdatert: 2022-08-04bibliografisk kontrollert

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