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Elucidating the nanostructure of small interfering RNA-loaded lipidoid-polymer hybrid nanoparticles

Aljabbari, Anas ; Lokras, Abhijeet Girish LU orcid ; Kirkensgaard, Jacob Judas Kain ; Rades, Thomas ; Franzyk, Henrik ; Thakur, Aneesh ; Zhang, Yibang and Foged, Camilla (2023) In Journal of Colloid and Interface Science 633. p.907-922
Abstract

We analyzed the structural and material properties of small interfering RNA (siRNA)-loaded lipid-polymer hybrid nanoparticles (LPNs) containing ionizable lipidoid and poly(dl-lactic-co-glycolic acid) (PLGA) using small-angle X-ray scattering, cryogenic transmission electron microscopy, polarized light microscopy, the Langmuir monolayer methodology, differential scanning calorimetry, and attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy. Scattering analyses showed that bulk lipidoid self-assemble into lamellar structures with a d-spacing of 38 Å, whereas lipidoid-siRNA lipoplexes display an in-plane lateral organization of siRNA in between lipidoid bilayers with a repeat distance of approximately 55 Å. The... (More)

We analyzed the structural and material properties of small interfering RNA (siRNA)-loaded lipid-polymer hybrid nanoparticles (LPNs) containing ionizable lipidoid and poly(dl-lactic-co-glycolic acid) (PLGA) using small-angle X-ray scattering, cryogenic transmission electron microscopy, polarized light microscopy, the Langmuir monolayer methodology, differential scanning calorimetry, and attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy. Scattering analyses showed that bulk lipidoid self-assemble into lamellar structures with a d-spacing of 38 Å, whereas lipidoid-siRNA lipoplexes display an in-plane lateral organization of siRNA in between lipidoid bilayers with a repeat distance of approximately 55 Å. The siRNA-loaded LPNs adopted a core-shell structure with an interaxial alignment of siRNA between lipidoid shell bilayers. Langmuir monolayer experiments showed a distinct interaction between the lipidoid headgroups and siRNA, which was dependent on buffer subphase pH. Thermal analyses suggested that PLGA and lipidoid interact, which was evident from a shift in the phase transition temperature of lipidoid, and the thermotropic phase behavior of lipidoid was affected by inclusion of siRNA. ATR-FTIR data confirmed the shift or disappearance of characteristic absorption bands of siRNA after lipidoid binding. In conclusion, siRNA-loaded LPNs display a core-shell structure, wherein the polymeric core functions as a colloid matrix support for siRNA-loaded lipidoid shell layers.

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author
; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
RNA, Small Interfering/chemistry, Polymers/chemistry, Nanoparticles/chemistry, Lactic Acid/chemistry
in
Journal of Colloid and Interface Science
volume
633
pages
907 - 922
publisher
Academic Press
external identifiers
  • pmid:36508398
  • scopus:85145491707
ISSN
0021-9797
DOI
10.1016/j.jcis.2022.11.141
language
English
LU publication?
no
additional info
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
id
aa255450-5f25-4579-b24f-cbe8687676d6
date added to LUP
2025-05-28 15:11:36
date last changed
2025-05-29 04:03:11
@article{aa255450-5f25-4579-b24f-cbe8687676d6,
  abstract     = {{<p>We analyzed the structural and material properties of small interfering RNA (siRNA)-loaded lipid-polymer hybrid nanoparticles (LPNs) containing ionizable lipidoid and poly(dl-lactic-co-glycolic acid) (PLGA) using small-angle X-ray scattering, cryogenic transmission electron microscopy, polarized light microscopy, the Langmuir monolayer methodology, differential scanning calorimetry, and attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy. Scattering analyses showed that bulk lipidoid self-assemble into lamellar structures with a d-spacing of 38 Å, whereas lipidoid-siRNA lipoplexes display an in-plane lateral organization of siRNA in between lipidoid bilayers with a repeat distance of approximately 55 Å. The siRNA-loaded LPNs adopted a core-shell structure with an interaxial alignment of siRNA between lipidoid shell bilayers. Langmuir monolayer experiments showed a distinct interaction between the lipidoid headgroups and siRNA, which was dependent on buffer subphase pH. Thermal analyses suggested that PLGA and lipidoid interact, which was evident from a shift in the phase transition temperature of lipidoid, and the thermotropic phase behavior of lipidoid was affected by inclusion of siRNA. ATR-FTIR data confirmed the shift or disappearance of characteristic absorption bands of siRNA after lipidoid binding. In conclusion, siRNA-loaded LPNs display a core-shell structure, wherein the polymeric core functions as a colloid matrix support for siRNA-loaded lipidoid shell layers.</p>}},
  author       = {{Aljabbari, Anas and Lokras, Abhijeet Girish and Kirkensgaard, Jacob Judas Kain and Rades, Thomas and Franzyk, Henrik and Thakur, Aneesh and Zhang, Yibang and Foged, Camilla}},
  issn         = {{0021-9797}},
  keywords     = {{RNA, Small Interfering/chemistry; Polymers/chemistry; Nanoparticles/chemistry; Lactic Acid/chemistry}},
  language     = {{eng}},
  pages        = {{907--922}},
  publisher    = {{Academic Press}},
  series       = {{Journal of Colloid and Interface Science}},
  title        = {{Elucidating the nanostructure of small interfering RNA-loaded lipidoid-polymer hybrid nanoparticles}},
  url          = {{http://dx.doi.org/10.1016/j.jcis.2022.11.141}},
  doi          = {{10.1016/j.jcis.2022.11.141}},
  volume       = {{633}},
  year         = {{2023}},
}