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  • 标题:Controlling DNA–nanoparticle serum interactions
  • 本地全文:下载
  • 作者:Kyryl Zagorovsky ; Leo Y. T. Chou ; Warren C. W. Chan
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2016
  • 卷号:113
  • 期号:48
  • 页码:13600-13605
  • DOI:10.1073/pnas.1610028113
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:SignificanceDNA-mediated nanoparticle assembly is an emerging concept to design drug delivery vehicles that can modify their structure or function in response to the in vivo environment. However, better understanding of their interactions with different tissues and organs is needed to establish specific design criteria. Here, we perform a systematic investigation of the molecular properties and mechanisms responsible for serum degradation of DNA-assembled structures. We show that the degradation process is determined by the combined contributions of the surface chemistry of nanoparticles and their supramolecular arrangement. The results also present a strategy for using physiological fluid degradation as the mechanism of controlled drug release. Our findings provide a general framework to study biological interactions of DNA nanostructures. 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.
  • 关键词:nanoparticle assembly ; DNA nanostructures ; serum stability ; serum resistance ; controlled cargo release
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