Polyalkylcyanoacrylate nanoparticles as polymeric carriers for antisense oligonucleotides

Area of Science:

• Polymer Science
• Nucleic Acid Chemistry
• Nanotechnology

Background:

• Oligonucleotides require carriers for effective cellular delivery.
• Nanoparticles offer potential as protective and delivery vehicles for biomolecules.

Purpose of the Study:

• To investigate the adsorption of oligothymidylates onto cyanoacrylate nanoparticles.
• To explore the role of hydrophobic cations in oligonucleotide-nanoparticle complexation.
• To assess the protective capabilities of these nanoparticles against enzymatic degradation.

Main Methods:

• Adsorption studies using oligothymidylates and polyisobutyl/polyisohexylcyanoacrylate nanoparticles.
• Utilized hydrophobic cations (tetraphenylphosphonium chloride, quaternary ammonium salts) for ion-pair formation.
• Determined carrier capacity and evaluated in vitro protection against snake venom phosphodiesterase.

Main Results:

• Oligonucleotide adsorption is mediated by ion pair formation between phosphate groups and hydrophobic cations.
• Adsorption efficiency depends on oligonucleotide length, nanoparticle type, cation hydrophobicity, and ionic concentration.
• Polyisohexylcyanoacrylate nanoparticles demonstrated a carrier capacity of 5 μmol/g for 16-nucleotide oligothymidylates with cetyltrimethylammonium bromide.
• Adsorbed oligothymidylates showed protection against 3'-exonuclease degradation.

Conclusions:

• Cyanoacrylate nanoparticles effectively carry and protect oligothymidylates via hydrophobic cation complexation.
• These nanoparticles represent a viable system for oligonucleotide delivery in cellular contexts.
• Potential for future in vivo applications in oligonucleotide-based therapies.