This is a page describing data taken during an experiment at the ISIS Neutron and Muon Source. Information about the ISIS Neutron and Muon Source can be found at https://www.isis.stfc.ac.uk.
Probing the internal structure of fluorinated lipid nanoparticles for gene delivery
Abstract: Gene therapy offers a promising approach to treat complex diseases such as cancer and neurological disorders. Due to the instability and degradability of nucleic acids (NAs), vectors are needed to cross cell membranes. Lipid nanoparticles (LNPs), used for siRNA and mRNA delivery, consist of a cationic ionizable lipid (CIL), cholesterol, a phospholipid, and a pegylated lipid. Despite their success, LNPs show low delivery efficacy (1 2%), with most NAs failing to reach the cytosol. Recently, fluorination of gene delivery components has been shown to boost cellular uptake and endosomal escape 3 10 fold for polymers and 30 50 fold for lipid-based carriers. Traditional long perfluoroalkyl chains are now being replaced by shorter, branched fluorinated groups for better biodistribution and sustainability. We therefore designed a novel fluorinated CIL (F-CIL-NMe2) with a short branched fluorinated tag per tail to be incorporated in LNP for improving their bio-nano interactions and improve NA release. Here we propose to study by SANS how the F-CIL-NMe2 incorporation affects the inner structure of LNP through contrast matching measurements.
Principal Investigator: Dr Francesca Baldelli Bombelli
Experimenter: Dr Anas Aljabbari
Experimenter: Professor Lars Lennart Castro Nilsson
Experimenter: Mr Hans Bolinsson
Local Contact: Dr Najet Mahmoudi
Experimenter: Ms Flavia Borrelli
Experimenter: Dr Federica Sebastiani
Experimenter: Mrs Martina Beccalli
DOI: 10.5286/ISIS.E.RB2610447
ISIS Experiment Number: RB2610447
| Part DOI | Instrument | Public release date | Download Link |
|---|---|---|---|
| 10.5286/ISIS.E.RB2610447-1 | SANS2D | 14 October 2029 | Download |
Publisher: STFC ISIS Neutron and Muon Source
Data format: RAW/Nexus
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Data Citation
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[author], [date], [title], [publisher],
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Dr Francesca Baldelli Bombelli et al; (2026): Probing the internal structure of fluorinated lipid nanoparticles for gene delivery, STFC ISIS Neutron and Muon Source, https://doi.org/10.5286/ISIS.E.RB2610447
Data is released under the CC-BY-4.0 license.