Controlling DNA–nanoparticle serum interactions
| Autor: | Leo Y. T. Chou, Warren C. W. Chan, Kyryl Zagorovsky |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Exonuclease
Serum Materials science Kinetics Oligonucleotides Nanoparticle Nanotechnology 02 engineering and technology 010402 general chemistry 01 natural sciences Polyethylene Glycols chemistry.chemical_compound Drug Delivery Systems In vivo PEG ratio Deoxyribonuclease I Humans DNA Cleavage Multidisciplinary biology Oligonucleotide DNA 021001 nanoscience & nanotechnology 0104 chemical sciences Nanostructures chemistry Physical Sciences Biophysics biology.protein Degradation (geology) Nanoparticles 0210 nano-technology |
| Popis: | Understanding the interaction of molecularly assembled nanoparticles with physiological fluids is critical to their use for in vivo delivery of drugs and contrast agents. Here, we systematically investigated the factors and mechanisms that govern the degradation of DNA on the nanoparticle surface in serum. We discovered that a higher DNA density, shorter oligonucleotides, and thicker PEG layer increased protection of DNA against serum degradation. Oligonucleotides on the surface of nanoparticles were highly resistant to DNase I endonucleases, and degradation was carried out exclusively by protein-mediated exonuclease cleavage and full-strand desorption. These results enabled the programming of the degradation rates of the DNA-assembled nanoparticle system from 0.1 to 0.7 h −1 and the engineering of superstructures that can release two different preloaded dye molecules with distinct kinetics and half-lives ranging from 3.3 to 9.8 h. This study provides a general framework for investigating the serum stability of DNA-containing nanostructures. The results advance our understanding of engineering principles for designing nanoparticle assemblies with controlled in vivo behavior and present a strategy for storage and multistage release of drugs and contrast agents that can facilitate the diagnosis and treatment of cancer and other diseases. |
| Databáze: | OpenAIRE |
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