Coupling Lipid Nanoparticle Structure and Automated Single-Particle Composition Analysis to Design Phospholipase-Responsive Nanocarriers.

Autor: Barriga HMG; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, SE-171 77, Sweden., Pence IJ; Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK., Holme MN; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, SE-171 77, Sweden.; Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK., Doutch JJ; ISIS Neutron and Muon Source, STFC, Rutherford Appleton Laboratory, Didcot, OX11 ODE, UK., Penders J; Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK., Nele V; Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK., Thomas MR; Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK., Carroni M; Department of Biochemistry and Biophysics, Science for Life Laboratory, Stockholm University, Stockholm, 171 65, Sweden., Stevens MM; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, SE-171 77, Sweden.; Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK.
Jazyk: angličtina
Zdroj: Advanced materials (Deerfield Beach, Fla.) [Adv Mater] 2022 Jul; Vol. 34 (26), pp. e2200839. Date of Electronic Publication: 2022 May 18.
DOI: 10.1002/adma.202200839
Abstrakt: 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.
(© 2022 The Authors. Advanced Materials published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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