Aljabbari Anas, Lokras Abhijeet Girish, Kirkensgaard Jacob Judas Kain, Rades Thomas, Franzyk Henrik, Thakur Aneesh, Zhang Yibang, Foged Camilla
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen Ø, Denmark.
Department of Food Science, Faculty of Science, University of Copenhagen, Rolighedsvej 26, 1958 Frederiksberg C, Denmark; Niels Bohr Institute, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen Ø, Denmark.
J Colloid Interface Sci. 2023 Mar;633:907-922. doi: 10.1016/j.jcis.2022.11.141. Epub 2022 Nov 28.
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.
我们使用小角X射线散射、低温透射电子显微镜、偏光显微镜、朗缪尔单层膜方法、差示扫描量热法和衰减全反射傅里叶变换红外（ATR-FTIR）光谱，分析了负载小干扰RNA（siRNA）的脂质-聚合物杂化纳米颗粒（LPNs）的结构和材料特性，该纳米颗粒含有可电离类脂和聚（dl-乳酸-共-乙醇酸）（PLGA）。散射分析表明，大量类脂自组装成d间距为38 Å的层状结构，而类脂-siRNA脂质复合物在类脂双层之间显示出siRNA的面内横向组织，重复距离约为55 Å。负载siRNA的LPNs采用核壳结构，类脂壳双层之间的siRNA呈轴间排列。朗缪尔单层膜实验表明，类脂头基与siRNA之间存在明显的相互作用，这取决于缓冲亚相的pH值。热分析表明PLGA和类脂相互作用，这从类脂相变温度的变化中可以明显看出，并且类脂的热致相行为受siRNA包含的影响。ATR-FTIR数据证实了类脂结合后siRNA特征吸收带的位移或消失。总之，负载siRNA的LPNs呈现核壳结构，其中聚合物核作为负载siRNA的类脂壳层的胶体基质支持物。
