Endogenous miRNA and K+ Co-Activated Dynamic Assembly of DNA Coacervates for Intracellular miRNA Imaging and Mitochondrial Intervention

• Published in: Analytical chemistry (Washington) Vol. 95; no. 37; pp. 14101 - 14110
• Main Authors: Sun, Wenyu, Yin, Jiajia, Liu, Liu, Wu, Zhicheng, Wang, Yihan, Liu, Tengfei, Xiong, Hongjie, Liu, Xiaohui, Wang, Xuemei, Jiang, Hui
• Format: Journal Article
• Language: English
• Published: Washington American Chemical Society 19.09.2023
• Subjects: Assembly; Cell membranes; Cellular manufacture; Chemistry; Colorimetry; Deoxyribonucleic acid; DNA; Hybridization; Intracellular; Medical imaging; Metabolism; Metastases; miRNA; Mitochondria; Potassium; Precision medicine
• ISSN: 0003-2700; 1520-6882
• DOI: 10.1021/acs.analchem.3c03053

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.