Binding of single stranded nucleic acids to cationic ligand functionalized gold nanoparticles

Area of Science:

• Nanotechnology
• Biophysics
• Molecular Biology

Background:

• Interactions between nanoparticles (NPs) and single-stranded nucleic acids (NAs) are crucial for gene delivery, nanomedicine, and nanotechnology.
• Understanding these interactions is key to developing advanced biomedical applications.

Purpose of the Study:

• To investigate the complexation of cationic ligand-functionalized gold nanoparticles with single-stranded DNA and RNA.
• To determine the influence of nanoparticle charge, NA sequence, and NA type on complexation and structural changes.

Main Methods:

• Utilized all-atom molecular dynamics simulations to model the interactions.
• Examined the binding affinities and structural consequences of nanoparticle-NA complexation.

Main Results:

• Complexation is primarily driven by nanoparticle charge, with electrostatic interactions between charged ligands and the NA backbone being dominant.
• Highly charged nanoparticles exhibit stronger binding and induce compaction of single-stranded NAs by disrupting intrastrand π-π stacking and hydrogen bonding.
• Poly-purine strands (polyA-DNA, polyA-RNA) show less structural alteration compared to poly-pyrimidine strands (polyT-DNA, polyU-RNA).

Conclusions:

• Cationic nanoparticles with a charge exceeding 30 can effectively control single-stranded NA structure.
• The degree of structural modification is dependent on both nanoparticle charge and the specific NA sequence.
• These findings offer insights for designing targeted nanocarriers for gene therapy and other biomedical applications.