College of Chemistry and Molecular Sciences, Wuhan University, 430072, Wuhan, P. R. China.
Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, Hubei Key Laboratory of Lipid Chemistry and Nutrition, Key Laboratory of Oilseeds Processing, Ministry of Agriculture, 430062, Wuhan, P. R. China.
Angew Chem Int Ed Engl. 2021 May 3;60(19):10766-10774. doi: 10.1002/anie.202101474. Epub 2021 Mar 31.
DNAzyme-based gene therapy holds immense prospects for effectively treating severe diseases, yet is constrained with inefficient delivery and unconditional activation. Herein, we designed a bioinspired self-catabolic DNA nanocapsule for sustaining tumor-specific cascade activation of therapeutic DNAzyme. The exquisite DNAzyme was temporarily masked by the self-excising DNAzyme in the hierarchical rolling circle replication (RCR) nanostructures, thus stayed in an inactive state in physiological fluids. Through the multivalent tumor-anchoring aptamer strands, the RCR nanocapsule was specifically accumulated in cancer cells and was sequentially activated for motivating the ultimate DNAzyme-mediated gene silencing via the intelligent stimuli-responsive cascade DNAzyme activation. By virtue of the programmable RCR assembly strategy, our compact DNAzyme nanoplatform shows great promise for developing versatile smart gene therapeutics and personalized nanomedicines.
基于 DNA 酶的基因治疗为有效治疗严重疾病带来了巨大的前景，但受到低效传递和无条件激活的限制。在这里，我们设计了一种受生物启发的自分解 DNA 纳米胶囊，用于持续进行肿瘤特异性级联激活治疗性 DNA 酶。在分级滚环复制（RCR）纳米结构中，精巧的 DNA 酶暂时被自我切除的 DNA 酶掩盖，因此在生理流体中处于非活性状态。通过多价肿瘤锚定适体链，RCR 纳米胶囊特异性地积聚在癌细胞中，并通过智能刺激响应级联 DNA 酶激活来依次激活，以激发最终的 DNA 酶介导的基因沉默。凭借可编程的 RCR 组装策略，我们紧凑的 DNA 酶纳米平台为开发多功能智能基因治疗和个性化纳米医学提供了广阔的前景。
