Controlling DNA-nanoparticle serum interactions.

Area of Science:

• Biomaterials Science
• Nanotechnology
• Molecular Biology

Background:

• Understanding nanoparticle-physiological fluid interactions is crucial for in vivo drug and contrast agent delivery.
• DNA-based nanostructures offer versatile platforms for biomedical applications.
• Serum stability is a key challenge for the in vivo performance of nanodelivery systems.

Purpose of the Study:

• To systematically investigate factors governing DNA degradation on nanoparticle surfaces in serum.
• To elucidate the mechanisms of DNA degradation in physiological fluids.
• To engineer DNA-nanoparticle systems with controlled degradation rates and drug release profiles.

Main Methods:

• Systematic investigation of DNA density, oligonucleotide length, and polyethylene glycol (PEG) layer thickness effects on DNA stability.
• Assessment of DNA degradation mechanisms, including endonuclease and exonuclease activity, and strand desorption.
• Programming degradation rates and engineering superstructures for controlled release of preloaded molecules.

Main Results:

• Higher DNA density, shorter oligonucleotides, and thicker PEG layers enhanced DNA protection against serum degradation.
• DNA on nanoparticle surfaces showed resistance to DNase I but was degraded by protein-mediated exonuclease cleavage and full-strand desorption.
• Degradation rates were programmed from 0.1 to 0.7 h⁻¹, and superstructures demonstrated distinct release kinetics with half-lives from 3.3 to 9.8 h.

Conclusions:

• A general framework for assessing serum stability of DNA-containing nanostructures was established.
• Engineering principles for designing nanoparticle assemblies with controlled in vivo behavior were advanced.
• A strategy for storage and multistage release of drugs and contrast agents for cancer diagnosis and treatment was presented.