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Metallo-Cubosomes: Zinc-Functionalized Cubic Nanoparticles for Therapeutic Nucleotide Delivery.
- Source :
-
Molecular pharmaceutics [Mol Pharm] 2019 Mar 04; Vol. 16 (3), pp. 978-986. Date of Electronic Publication: 2019 Feb 01. - Publication Year :
- 2019
-
Abstract
- 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 <subscript>2</subscript> BDPA)) complexes admixed with glycerol monooleate (GMO). The zinc metallo-cubosomes showed the high affinity to siRNA through interaction between Zn <subscript>2</subscript> 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 <subscript>2</subscript> BDPA lipid derivatives can be loaded into GMO cubosomes and the introduction of Zn <subscript>2</subscript> 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.
- Subjects :
- A549 Cells
Animals
CHO Cells
Cell Survival drug effects
Cricetulus
Dynamic Light Scattering
Gene Silencing
Humans
Microscopy, Electron, Transmission
Organometallic Compounds chemical synthesis
Phase Transition
Picolinic Acids chemical synthesis
Protein Binding
RNA, Small Interfering administration & dosage
RNA, Small Interfering therapeutic use
Scattering, Small Angle
X-Ray Diffraction
Drug Delivery Systems
Glycerides chemistry
Nanoparticles chemistry
Organometallic Compounds chemistry
Picolinic Acids chemistry
RNA, Small Interfering chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1543-8392
- Volume :
- 16
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Molecular pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 30648870
- Full Text :
- https://doi.org/10.1021/acs.molpharmaceut.8b00890