Tailored Nucleic Acid Architectures at Gold Surfaces for Controlled Therapeutic Release

Area of Science:

• Nanotechnology
• Biomaterials Science
• Drug Delivery Systems

Background:

• Nucleic acids, particularly DNA, are adaptable for creating smart nanocarriers for controlled therapeutic delivery.
• DNA-gated release utilizes DNA oligonucleotides to physically impede drug release from porous nanoparticles.
• This study explores extending DNA-gated release to drugs surface-bound on DNA-capped gold nanoparticles (AuNPs).

Purpose of the Study:

• To investigate how DNA monolayer thickness and hybridization states on AuNPs affect the release of surface-bound drugs.
• To determine the influence of DNA surface architecture on drug release kinetics from AuNPs.
• To explore the potential of DNA-capped AuNPs for improved biological availability of surface-bound drugs.

Main Methods:

• Utilized quartz crystal microbalance with dissipation (QCM-D) to study DNA layers on planar gold surfaces.
• Employed dynamic light scattering (DLS) to analyze DNA layer architectures on AuNPs.
• Investigated the effect of different DNA layer architectures on the release rate of a template drug bound to the gold surface.

Main Results:

• Varying DNA architectures on AuNPs significantly alter drug release rates.
• Folded or randomly coiled DNA sequences act as physical barriers, slowing drug diffusion and release.
• Upright DNA monolayers facilitate quicker drug release, with longer single-stranded DNA further slowing release.
• Even upright DNA layers can impede drug diffusion for longer sequences, suggesting architecture is key.

Conclusions:

• The architecture of the DNA layer, dictated by the orientation of individual DNA molecules (folded, coiled, or upright), critically influences drug diffusion and release rates from AuNPs.
• This DNA-gated release mechanism on surface-bound drugs holds promise for enhancing the biological availability of therapeutics delivered via solid, DNA-capped nanoparticles.