ISIS Neutron and Muon Source Data Journal

Elucidating the Structural Basis of Ionizable Lipid Nanocarriers for Targeted siRNA Delivery

Abstract: Ionizable lipid nanocarriers (ILNCs) composed of POPC, DODMA, cholesterol, and DOPE-PEG2000-Maleimide-T7 combine biocompatibility, structural stability, and site-specific conjugation of the T7 peptide targeting the human transferrin receptor. These systems show superior performance compared to their cationic analogues containing DOTAP, yet the structural basis for this improvement remains unclear. This proposal aims to elucidate how the ionizable lipid DODMA modulates bilayer organization and how pH variations and siRNA encapsulation influence the structure of ILNCs. SANS with contrast variation between hydrogenated and deuterated lipids will be used to compare ILNCs and their cationic analogues, focusing on bilayer thickness, T7 exposure, and pH-dependent rearrangements. The results will clarify how lipid ionization and peptide functionalization affect membrane organization, guiding the design of efficient targeted nanocarriers for gene delivery.

Principal Investigator: Professor Luigi Paduano
Experimenter: Dr Noemi Gallucci
Experimenter: Mr Alessandro Cangiano
Local Contact: Dr Leide Cavalcanti
Experimenter: Mrs Ilaria De Cristofaro

DOI: 10.5286/ISIS.E.RB2610246

ISIS Experiment Number: RB2610246

Publisher: STFC ISIS Neutron and Muon Source

Data format: RAW/Nexus
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Data Citation

The recommended format for citing this dataset in a research publication is as:
[author], [date], [title], [publisher], [doi]

For Example:
Professor Luigi Paduano et al; (2026): Elucidating the Structural Basis of Ionizable Lipid Nanocarriers for Targeted siRNA Delivery, STFC ISIS Neutron and Muon Source, https://doi.org/10.5286/ISIS.E.RB2610246

Data is released under the CC-BY-4.0 license.