Wu Xue, Bai Huijie, Jiang Lingfeng, Mao Cuiping, Li Yi, Li Diangeng, Wang Yong, Liu Shan, Guo Jinhong
Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, 400016, Chongqing, China.
Department of Academic Research, Beijing Ditan Hospital, Capital Medical University, National Center for Infectious Diseases (Beijing), 100015, Beijing, China.
Microsyst Nanoeng. 2025 May 27;11(1):108. doi: 10.1038/s41378-025-00927-1.
Sensitive and rapid imaging of intracellular cancer-related miRNA holds great potential for early diagnosis and treatment monitoring of cancer. However, most imaging probes are constructed on nanoparticles that rely on passive diffusion to interact and bind with the target substance, resulting a long response time and a low target recognition capability due to the solution viscous resistance. Herein, we reported a DNA tetrahedral-modified magnetic nanorobotic probe (MNP) that performed framework nucleic acid-located catalytic hairpin assembly (CHA) reaction on the surface of magnetically driven nanorobot. The tetrahedral structure not only endowed the MNP with extremely high structural stability and perfect cell-uptake performance, but its spatial confinement effect made the signal amplification of the hairpin cascade more rapid and efficient. Additionally, the active movement of MNPs enhanced the micro-mixing of fluids and accelerated target capture, significantly reducing reaction time and improving reaction kinetics. This strategy exhibited the enhanced fluorescence signal and can accurately distinguish between miR-21 and various other miRNA sequences. Moreover, the feasibility and versatility of MNPs were also successfully verified in normal and various cancer cells imaging. Therefore, the proposed MNPs are promising candidates for the detection of intracellular biomarkers and extend the design space of self-propelled micro/nanorobots in the field of cancer diagnosis and therapy.
对细胞内癌症相关微小RNA进行灵敏且快速的成像，在癌症的早期诊断和治疗监测方面具有巨大潜力。然而，大多数成像探针是基于纳米颗粒构建的，这些纳米颗粒依靠被动扩散与目标物质相互作用并结合，由于溶液的粘性阻力，导致响应时间长且目标识别能力低。在此，我们报道了一种DNA四面体修饰的磁性纳米机器人探针（MNP），其在磁驱动纳米机器人表面进行基于框架核酸的催化发夹组装（CHA）反应。四面体结构不仅赋予MNP极高的结构稳定性和完美的细胞摄取性能，而且其空间限制效应使发夹级联的信号放大更加快速和高效。此外，MNP的主动运动增强了流体的微混合并加速了目标捕获，显著缩短了反应时间并改善了反应动力学。该策略表现出增强的荧光信号，并且能够准确区分miR-21与其他各种微小RNA序列。此外，MNP在正常细胞和各种癌细胞成像中的可行性和通用性也得到了成功验证。因此，所提出的MNP有望成为检测细胞内生物标志物的候选者，并扩展了自驱动微/纳米机器人在癌症诊断和治疗领域的设计空间。
