Nucleic acid-based supramolecular structures: vesicular spherical nucleic acids from a non-phospholipid nucleolipid

Area of Science:

• Biomaterials Science
• Supramolecular Chemistry
• Nucleic Acid Nanotechnology

Background:

• Spherical nucleic acids (SNAs) are nucleic acid-based supramolecular structures with diverse applications.
• Conventional SNAs often face challenges in stability and delivery efficiency.

Purpose of the Study:

• To synthesize and characterize novel vesicular spherical nucleic acids (vSNAs) using a non-phospholipid nucleolipid.
• To evaluate the self-assembly properties and potential applications of these vSNAs in drug delivery and diagnostics.

Main Methods:

• Synthesis of a nucleolipid via click chemistry between a functionalized oligonucleotide and a lipid-like molecule.
• Self-assembly of nucleolipids into vesicular structures in aqueous solution and via intercalation into liposomes.
• Characterization using dynamic, static, and electrophoretic light scattering, and cryogenic transmission electron microscopy (TEM).

Main Results:

• Spontaneous formation of nanosized unilamellar vesicles with an interdigitated bilayer structure.
• Successful intercalation of nucleolipids into pre-formed liposomes.
• vSNAs demonstrated efficient cellular internalization without transfection agents.
• Enhanced colloidal and nuclease stability compared to reference SNAs.

Conclusions:

• The novel nucleolipid enables the formation of stable and functional vesicular spherical nucleic acids.
• These vSNAs hold significant potential for advanced drug delivery, diagnostics, and therapeutic applications.
• The findings contribute to the development of next-generation nucleic acid-based nanostructures.