TY - JOUR
T1 - Elucidating the nanostructure of small interfering RNA-loaded lipidoid-polymer hybrid nanoparticles
AU - Aljabbari, Anas
AU - Lokras, Abhijeet Girish
AU - Kirkensgaard, Jacob Judas Kain
AU - Rades, Thomas
AU - Franzyk, Henrik
AU - Thakur, Aneesh
AU - Zhang, Yibang
AU - Foged, Camilla
N1 - Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
U2 - 10.1016/j.jcis.2022.11.141
DO - 10.1016/j.jcis.2022.11.141
M3 - Journal article
C2 - 36508398
VL - 633
SP - 907
EP - 922
JO - Journal of Colloid and Interface Science
JF - Journal of Colloid and Interface Science
SN - 0021-9797
ER -