National Nano Center uses nucleic acid self-assembly structure to achieve gene drug delivery
November 01, 2018 Source: Chinese Academy of Sciences
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];Gene therapy is a research strategy that achieves relevant treatments at the most fundamental level of disease development. Gene therapy drugs that are now on the market are mostly based on viruses for gene delivery. The introduction of viral vectors will undoubtedly raise concerns about the biosafety of such therapeutic systems. Therefore, the development of biocompatible gene delivery vectors is becoming more and more important and has become one of the challenging frontier topics. The DNA origami nanotechnology developed in recent years is a unique bottom-up self-assembled nanotechnology that can be used to design and prepare self-assembled nanostructures with various sizes and morphology controllable. DNA nanostructures and gene drugs have chemical compositional consistency and show significant advantages in the design of biocompatible gene delivery vectors.
Since 2012, the research team of the National Nanoscience Center of the Chinese Academy of Sciences, Ding Baoquan, has constructed a series of drug delivery vehicles based on self-assembled multifunctional nucleic acid nanostructures. The drug components delivered relate to small molecule drugs for chemotherapy (J. Am. Chem. Soc. 2012, 134, 13396; ACS Nano 2014, 8, 6633), photothermotherapy nanoparticle drugs (Small 2015, 11, 5134; Adv Mater. 2016, 28, 10000), Functional Proteins (Nat. Biotechnol. 2018, 36, 258), and Nucleic Acids (ACS Appl. Mater. Interfaces 2017, 9, 20324; Nano Lett. 2018, 18 , 3328). This multifunctional nucleic acid nano drug delivery system exhibits very good tumor targeting and biocompatibility and can serve as a new platform for disease diagnosis and treatment. In the recently published research work, Ding Baoquan's research group used the DNA origami structure as the carrier for the first time to achieve the co-delivery of the chemotherapy drug doxorubicin and the linear micro-hairpin RNA transcription template efficiently and controllably, and completed the combination of chemotherapy and gene therapy. medicine. The research was published online in the journal A Tailored DNA Nanoplatform for Synergistic RNAi-/Chemo- Therapy of Multidrug-Resistant Tumors (Angew. Chem. Int. Ed. 2018, DOI: 10.1002/anie.201809452) ).
Gene therapy in the field of cancer treatment has been widely reported, and gene delivery is mostly achieved by various types of cationic liposome, high molecular polymer and inorganic nanoparticles. Multifunctional DNA nanostructures are well-suited for the delivery of gene-based drugs as a biocompatible nanocarrier. The targeted modified triangular DNA origami structure is used as a carrier, and the high-efficiency loading of the chemotherapy drug doxorubicin is first achieved by inter-base intercalation. Subsequently, a linear small hairpin RNA transcription template targeting multidrug resistance-related genes (P glycoprotein and survivin) was ligated using a base-pair pairing strategy between nucleic acid strands. The DNA nano drug delivery system co-loaded by such chemotherapeutic drugs and gene drugs can achieve targeted delivery of doxorubicin-resistant breast cancer tumor cells by modified nucleic acid aptamers. The controlled release of doxorubicin and gene drugs was achieved by intracellular pH response and reducing atmosphere, and the expression of P glycoprotein and survivin was down-regulated by RNA interference to achieve killing of tumor cells. The results of mouse in vivo experiments show that this kind of DNA nano drug delivery system shows very good tumor targeting and biocompatibility, and can produce significant therapeutic effects on drug resistant breast cancer tumor models. The study is based on the natural nucleic acid structure of the biological system, and achieves the combined administration of chemotherapy and gene therapy, providing a new research strategy for the treatment of diseases such as malignant tumors.
The first author of the paper is Liu Jianbing, assistant researcher of the National Nano Center. The author of the communication is Ding Baoquan. The research was supported by the National Natural Science Foundation of China and the Key Research Program of the Frontier Science of the Chinese Academy of Sciences.
Figure: DNA origami structure loaded with chemotherapy drugs and gene drugs, targeting drug-resistant tumor cells, to achieve drug-resistant tumor growth inhibition
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