State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, P. R. China.
Anal Chem. 2023 Sep 19;95(37):14101-14110. doi: 10.1021/acs.analchem.3c03053. Epub 2023 Sep 6.
Intracellular dynamic assembly of DNA structures may be beneficial for the development of multifunctional nanoplatforms for the regulation of cell behaviors, providing new strategies for disease diagnosis and intervention. Herein, we propose the dynamic assembly of DNA coacervates in living cells triggered by miRNA-21 and K, which can be used for both miRNA imaging and mitochondrial intervention. The rationale is that miRNA-21 can trigger the hybridization chain reaction to generate G-quadruplex precursors, and K can mediate the assembly of G-quadruplex-based coacervates, allowing the colorimetric detection of miRNA-21 ranging from 10 pM to 10 μM. Moreover, the as-formed DNA coacervates can specifically target mitochondria in MCF-7 breast cancer cells using the MCF-7 cell membrane as delivery carriers, which further act as an anionic shielding to inhibit communication between mitochondria and environments, with a significant inhibitory effect on ATP production and cellular migration behaviors. This work provides an ideal multifunctional nanoplatform for rationally interfering with cellular metabolism and migration behaviors through the dynamic assembly of DNA coacervates mediated by endogenous molecules, which has a large number of potential applications in the biomedical field, especially theranostics for cancer metastasis.
DNA 结构的细胞内动态组装可能有益于开发多功能纳米平台以调节细胞行为，为疾病诊断和干预提供新策略。在此，我们提出了由 miRNA-21 和 K 触发的活细胞中 DNA 凝聚物的动态组装，可用于 miRNA 成像和线粒体干预。其原理是，miRNA-21 可以触发杂交链式反应产生 G-四链体前体，而 K 可以介导基于 G-四链体的凝聚物的组装，从而可以对 10 pM 至 10 μM 范围内的 miRNA-21 进行比色检测。此外，形成的 DNA 凝聚物可以使用 MCF-7 细胞膜作为递送载体，特异性靶向 MCF-7 乳腺癌细胞中的线粒体，进一步作为阴离子屏蔽物抑制线粒体与环境之间的通讯，对 ATP 产生和细胞迁移行为具有显著的抑制作用。这项工作提供了一个理想的多功能纳米平台，通过内源性分子介导的 DNA 凝聚物的动态组装，可以合理地干扰细胞代谢和迁移行为，在生物医学领域有大量潜在的应用，特别是癌症转移的治疗学。
