Huang Ping, Tang Xiaoqi, Zhao Shuang, Luo Jie, Tang Yu, Wang Binpan, Xie Zuowei, Wu Xianlan, Xie Shuang, Chen Ming, Chang Kai
Department of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), 30 Gaotanyan, Shapingba District, Chongqing 400038, P. R. China.
College of Pharmacy and Laboratory Medicine, Third Military Medical University (Army Medical University), 30 Gaotanyan, Shapingba District, Chongqing 400038, P. R. China.
Theranostics. 2025 Mar 21;15(10):4638-4653. doi: 10.7150/thno.105762. eCollection 2025.
Mitochondrial miRNAs (mitomiRs) are crucial regulators of mitochondrial functions and play pivotal roles in tumorigenesis and cancer progression. Nevertheless, direct monitoring mitomiRs and regulating mitochondrial function at the subcellular level remains challenging. In this study, we present a versatile DNA framework-based nanorobot for synchronous ultrasensitive detection of mitochondrial miRNAs (mitomiRs) and modulation of the mitochondria-associated apoptosis process. The DNA nanorobot features a tetrahedral nucleic acid framework as its structural body, two DNA hairpins (H1 and H2) as functional arms, and a mitochondria-targeting triphenylphosphine (TPP) group as the command center. The DNA nanorobot was comprehensively characterized for its morphological properties, mitochondria-targeting capacity, mitomiRs detection performance, DOX-loading and release behaviors, and antineoplastic effects both . Upon recognizing mitomiRs, the arms of the DNA nanorobot activate and trigger spatially restricted catalytic hairpin assembly (CHA) reactions with accelerated kinetics to generate amplified fluorescence signals. Additionally, the lipophilic anticancer drug doxorubicin (DOX) encapsulated within the DNA nanorobot induces reactive oxygen species (ROS) production, leading to mitochondria damage and promoting mitochondria-associated apoptosis in tumor cells. This newly developed DNA nanorobot provides a multifunctional platform for precise mitochondria-targeted diagnosis and enhanced therapeutic efficacy, advancing innovative strategies for mitochondria-focused tumor diagnosis and treatment.
线粒体微RNA（mitomiRs）是线粒体功能的关键调节因子，在肿瘤发生和癌症进展中起关键作用。然而，在亚细胞水平直接监测mitomiRs并调节线粒体功能仍然具有挑战性。在本研究中，我们提出了一种基于多功能DNA框架的纳米机器人，用于同步超灵敏检测线粒体微RNA（mitomiRs）以及调节线粒体相关的凋亡过程。该DNA纳米机器人以四面体核酸框架作为其结构体，两个DNA发夹（H1和H2）作为功能臂，以及一个靶向线粒体的三苯基膦（TPP）基团作为指挥中心。对该DNA纳米机器人的形态特性、线粒体靶向能力、mitomiRs检测性能、阿霉素负载和释放行为以及抗肿瘤作用进行了全面表征。在识别mitomiRs后，DNA纳米机器人的臂激活并触发空间受限的催化发夹组装（CHA）反应，其动力学加速，以产生放大的荧光信号。此外，封装在DNA纳米机器人内的亲脂性抗癌药物阿霉素（DOX）诱导活性氧（ROS）产生，导致线粒体损伤并促进肿瘤细胞中线粒体相关的凋亡。这种新开发的DNA纳米机器人为精确的线粒体靶向诊断和增强的治疗效果提供了一个多功能平台，推动了针对线粒体的肿瘤诊断和治疗的创新策略。
