Coupling Lipid Nanoparticle Structure and Automated Single‐Particle Composition Analysis to Design Phospholipase‐Responsive Nanocarriers
Year: 2022
Type: article
Abstract: 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.
Source: Advanced Materials
Language: English
Subfield: Biomaterials
Field: Materials Science
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $5,100
Funders: National Science Foundation, Whitaker International Program, Diamond Light Source, Kempe Foundation, Royal Academy of Engineering, European Commission, Rosetrees Trust, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Umeå Universitet, Kempestiftelserna, Stockholms Universitet, Science for Life Laboratory, Horizon 2020 Framework Programme, Engineering and Physical Sciences Research Council, Science and Technology Facilities Council, Division of Materials Research
Awards: Hybrid Vesicles for Cardiovascular Therapeutics, G1331437543, G1430250911, G1689194922, G263695037, G2650702889, G3108985476, G3537589354, G4221288801, G4310665315, G434337789, G4937468798, G5045220161, An innovative class of nanoparticles (“SmartCubes”) for the targeted delivery of protein therapeutics, G5170841131, G5190930545, G5214689270, G5586684623, Bio-functionalised Nanomaterials for Ultrasensitive Biosensing, Nanomedicine: an integrative approach, G5996562161, World class Science and Innovation with Neutrons in Europe 2020 – SINE2020, G6271517897, IMR-MIP DANSE - Distributed Data Analysis for Neutron Scattering Experiments - CNST, G7619790591, Targeting atherosclerosis: Raman-spectroscopy validated, triggered release of drugs from de novo phospholipid-incorporating liposomes by sphingomyelinase enzymatic degradation of the membrane bilayer, G7892797065, G789883748, EPSRC IRC in Early-Warning Sensing Systems for Infectious Diseases, G8380713174, i-sense: EPSRC IRC in Agile Early Warning Sensing Systems for Infectious Diseases and Antimicrobial Resistance
OpenAlex ID: W4220994635