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.