@article{Yu2026, 
author = {Wenyan Yu and Jiahui Su and Yuting Li and Wei Liu and Zigang Dong and Jinjin Shi},
title = {Ratio-tunable nucleic acid nanohybrids enable precision therapy for esophageal squamous cell carcinoma},
year = {2026},
journal = {Nano Research},
volume = {19},
number = {6},
pages = {94908592},
keywords = {gene therapy, esophageal squamous cell carcinoma, nucleic acid nanohybrid, dual-gene silencing, DNAzymes},
url = {https://www.sciopen.com/article/10.26599/NR.2026.94908592},
doi = {10.26599/NR.2026.94908592},
abstract = {Esophageal squamous cell carcinoma (ESCC) progression is strongly associated with the overexpression of bromodomain-containing protein 4 (BRD4) and syndecan-binding protein (SDCBP), identifying them as promising therapeutic targets. Conventional inhibitors, however, are frequently constrained by off-target effects and insufficient tumor specificity. Gene therapy, with nucleic acid drugs as its core, offers the advantage of directly modulating disease-causing gene expression, therefore overcoming these limitations. Therefore, this study aims to develop a multifunctional nucleic acid nanohybrid integrating an ESCC-specific aptamer, BRD4 DNAzyme (BDz), and SDCBP DNAzyme (SDz) for tumor-targeted therapy. This nanohybrid is engineered to respond to the acidic lysosomal environment by releasing BDz and SDz, enabling dual gene silencing, while tumor-specific delivery is mediated by the aptamer. Systematic adjustment of the molar ratios of BDz, SDz, and aptamer A components revealed that a 3:2:1 ratio produced optimal antitumor efficacy. This approach establishes a tunable-ratio dual-DNAzyme delivery platform that maximizes synergistic therapeutic effects while balancing targeted delivery with effective gene silencing, achieving precise dual-target therapy against ESCC. The results provide a base for the development of customizable multifunctional precision gene therapies.}
}