期刊
MOLECULAR PHARMACEUTICS
卷 16, 期 3, 页码 978-986出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.8b00890
关键词
cubosomes; nanoparticles; siRNA delivery; self-assembly
资金
- University of Melbourne-CSIRO PhD scholarship
Development of an effective and potent RNA delivery system remains a challenge for the clinical application of RNA therapeutics. Herein, we describe the development of an RNA delivery platform derived from self-assembled bicontinuous cubic lyotropic liquid crystalline phases, functionalized with zinc coordinated lipids. These metallo-cubosomes were prepared from a series of novel lipidic zinc(II)-bis(dipicolylamine) (Zn(2)BDPA)) complexes admixed with glycerol monooleate (GMO). The zinc metallo-cubosomes showed the high affinity to siRNA through interaction between Zn(2)BDPA and the phosphate groups of RNA molecules. Using a combination of dynamic light scattering (DLS), small-angle X-ray scattering (SAXS), and cryogenic transmission electron microscopy (cryo-TEM), we demonstrated that a variety of Zn(2)BDPA lipid derivatives can be loaded into GMO cubosomes and the introduction of Zn(2)BDPA lipids effected an internal cubic phase transition of the resulting metallo-cubosomes. The findings of this study lay the foundations for the development of a new class of noncationic lipid-based encapsulation systems, metallo-cubosomes for RNA therapeutic delivery.
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