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Versatile Catalytic Deoxyribozyme Vehicles for Multimodal Imaging-Guided Efficient Gene Regulation and Photothermal Therapy
ACS Nano ( IF 15.8 ) Pub Date : 2018-12-12 00:00:00 , DOI: 10.1021/acsnano.8b08101 Jie Feng 1 , Zhen Xu 1 , Feng Liu 1 , Yun Zhao 1 , Wenqian Yu 1 , Min Pan 1 , Fuan Wang 1 , Xiaoqing Liu 1
ACS Nano ( IF 15.8 ) Pub Date : 2018-12-12 00:00:00 , DOI: 10.1021/acsnano.8b08101 Jie Feng 1 , Zhen Xu 1 , Feng Liu 1 , Yun Zhao 1 , Wenqian Yu 1 , Min Pan 1 , Fuan Wang 1 , Xiaoqing Liu 1
Affiliation
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Catalytic deoxyribozyme has great potential for gene regulation, but the poor efficiency of the cleavage of mRNA and the lack of versatile DNAzyme vehicles remain big challenges for potent gene therapy. By the rational designing of a diverse vehicle of polydopamine-Mn2+ nanoparticles (MnPDA), we demonstrate that MnPDA has integrated functions as an effective DNAzyme delivery vector, a self-generation source of DNAzyme cofactor for catalytic mRNA cleavage, and an inherent therapeutic photothermal agent as well as contrast agent for photoacoustic and magnetic resonance imaging. Specifically, the DNAzyme-MnPDA nanosystem protects catalytic deoxyribozyme from degradation and enhances cellular uptake efficiency. In the presence of intracellular glutathione, the nanoparticles are able to in situ generate free Mn2+ as a cofactor of DNAzyme to effectively trigger the catalytic cleavage of mRNA for gene silencing. In addition, the nanosystem shows high photothermal conversion efficiency and excellent stability against photothermal processing and degradation in complex environments. Unlike previous DNAzyme delivery vehicles, this vehicle exhibits diverse functionalities for potent gene regulation, allowing multimodal imaging-guided synergetic gene regulation and photothermal therapy both in vitro and in vivo.
中文翻译：
多功能催化脱氧核酶载体，用于多模式成像引导的高效基因调控和光热疗法
催化脱氧核酶具有巨大的基因调控潜力，但是有效的基因治疗仍面临着巨大的挑战，即mRNA切割效率低下以及缺乏通用的DNAzyme载体。通过合理设计聚多巴胺-Mn 2+纳米粒子（MnPDA）的多种载体，我们证明MnPDA具有作为有效的DNAzyme传递载体，用于催化mRNA切割的DNAzyme辅因子的自生来源和固有治疗作用的整合功能。用于光声和磁共振成像的光热剂和造影剂。具体而言，DNAzyme-MnPDA纳米系统可保护催化脱氧核酶免于降解并提高细胞摄取效率。在细胞内谷胱甘肽存在下，纳米颗粒能够原位产生游离的Mn 2+作为DNAzyme的辅助因子，从而有效地触发mRNA的催化裂解，从而实现基因沉默。此外，纳米系统显示出高的光热转化效率，并且在复杂环境中具有出色的抗光热加工和降解稳定性。与以前的DNAzyme传递载体不同，该载体展现出强大的基因调控功能，可在体外和体内进行多模式成像引导的协同基因调控和光热疗法。
更新日期：2018-12-12
中文翻译：
多功能催化脱氧核酶载体，用于多模式成像引导的高效基因调控和光热疗法
催化脱氧核酶具有巨大的基因调控潜力，但是有效的基因治疗仍面临着巨大的挑战，即mRNA切割效率低下以及缺乏通用的DNAzyme载体。通过合理设计聚多巴胺-Mn 2+纳米粒子（MnPDA）的多种载体，我们证明MnPDA具有作为有效的DNAzyme传递载体，用于催化mRNA切割的DNAzyme辅因子的自生来源和固有治疗作用的整合功能。用于光声和磁共振成像的光热剂和造影剂。具体而言，DNAzyme-MnPDA纳米系统可保护催化脱氧核酶免于降解并提高细胞摄取效率。在细胞内谷胱甘肽存在下，纳米颗粒能够原位产生游离的Mn 2+作为DNAzyme的辅助因子，从而有效地触发mRNA的催化裂解，从而实现基因沉默。此外，纳米系统显示出高的光热转化效率，并且在复杂环境中具有出色的抗光热加工和降解稳定性。与以前的DNAzyme传递载体不同，该载体展现出强大的基因调控功能，可在体外和体内进行多模式成像引导的协同基因调控和光热疗法。
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