Versatile Catalytic Deoxyribozyme Vehicles for Multimodal Imaging-Guided Efficient Gene Regulation and Photothermal Therapy
Versatile Catalytic Deoxyribozyme Vehicles for Multimodal Imaging-Guided Efficient Gene Regulation and Photothermal Therapy
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用于多模态成像引导的高效基因调控和光热治疗的多功能催化脱氧核酶载体
DOI：
10.1021/acsnano.8b08101
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发表时间：
2018-12-01
期刊：
影响因子：
17.1
通讯作者：
Liu, Xiaoqing
中科院分区：
文献类型：
--
作者：
Feng, Jie;Xu, Zhen;Liu, Xiaoqing
催化脱氧核酶在基因调控方面具有巨大的潜力，但其对mRNA的裂解效率较低，且缺乏通用的载体，仍然是有效基因治疗的一大挑战。通过合理设计多种载体的聚多巴胺- mn2 +纳米颗粒（MnPDA），我们证明了MnPDA具有综合的功能，作为一个有效的DNAzyme传递载体，一个DNAzyme辅助因子的自生成源，催化mRNA裂解，以及一个固有的治疗光热剂和光声和磁共振成像造影剂。具体来说，DNAzyme-MnPDA纳米系统保护催化脱氧核酶免受降解，提高细胞摄取效率。在细胞内谷胱甘肽存在的情况下，纳米颗粒能够原位生成游离的Mn2+作为DNAzyme的辅助因子，有效地触发mRNA的催化裂解，从而实现基因沉默。此外，该纳米体系具有较高的光热转换效率和良好的稳定性，在复杂的环境中不受光热加工和降解的影响。与以前的DNAzyme递送载体不同，该载体具有多种功能，可进行有效的基因调控，允许体外和体内多模式成像引导的协同基因调控和光热治疗。
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.