Triplex DNA Nanoswitch for pH-Sensitive Release of Multiple Cancer Drugs
Triplex DNA Nanoswitch for pH-Sensitive Release of Multiple Cancer Drugs
复制标题
用于多种癌症药物 pH 敏感释放的三重 DNA 纳米开关
DOI：
10.1021/acsnano.9b03846
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发表时间：
2019-06-01
期刊：
影响因子：
17.1
通讯作者：
Zhu, Xiaoli
中科院分区：
文献类型：
--
作者：
Chen, Xiaoxia;Chen, Tianshu;Zhu, Xiaoli
一种基于DNA的刺激响应性药物递送系统已经开发用于协同癌症治疗。该系统是建立在一个三链DNA纳米开关能够精确地响应pH值的变化范围类似于5.0-7.0。在细胞外中性pH空间，DNA纳米开关保持线性构象，同时固定多种治疗剂，如小分子和反义化合物。在通过内吞作用靶向癌细胞摄取后，酸性细胞内隔室内的纳米开关经历从线性到三链体的构象变化，导致治疗组合的智能释放。这种刺激响应药物递送系统不依赖于人工响应材料，使其具有生物相容性。此外，它能够同时递送多种治疗剂以增强疗效。使用荷瘤小鼠模型，我们显示了有效的基因沉默和显着抑制肿瘤生长静脉注射后的智能纳米开关，提供了组合癌症治疗的机会。
A DNA-based stimulus-responsive drug delivery system for synergetic cancer therapy has been developed. The system is built on a triplex-DNA nano switch capable of precisely responding to pH variations in the range of similar to 5.0-7.0. In extracellular neutral pH space, the DNA nanoswitch keeps a linear conformation, immobilizing multiple therapeutics such as small molecules and antisense compounds simultaneously. Following targeted cancer cell uptake via endocytosis, the nanoswitch inside acidic intracellular compartments goes through a conformational change from linear to triplex, leading to smart release of the therapeutic combination. This stimuli responsive drug delivery system does not rely on artificial responsive materials, making it biocompatible. Furthermore, it enables simultaneous delivery of multiple therapeutics for enhanced efficacy. Using tumor-bearing mouse models, we show efficient gene silencing and significant inhibition of tumor growth upon intravenous administration of the smart nanoswitch, providing opportunities for combinatorial cancer therapy.