Jia Bin, Ge Jingru, Ma Yuxuan, Sun Xiaolei, Li Zhe, Jiang Shuoxing, Yu Hanyang
State Key Laboratory of Coordination Chemistry, Department of Biomedical Engineering, College of Engineering and Applied Sciences, Chemistry and Biomedicine Innovation Center (ChemBIC), ChemBioMed Interdisciplinary Research Center, Nanjing University, Nanjing, Jiangsu, 210023, P. R. China.
State Key Laboratory of Analytical Chemistry for Life Science, Department of Biomedical Engineering, College of Engineering and Applied Sciences, Nanjing University, Nanjing, Jiangsu, 210023, P. R. China.
Angew Chem Int Ed Engl. 2024 Dec 24:e202421022. doi: 10.1002/anie.202421022.
Biological systems utilize precise spatial organization to facilitate and regulate information transmission within signaling networks. Inspired by this, artificial scaffolds that enable delicate spatial arrangements are desirable to increase the local concentration of reactants, expedite specific interactions, and minimize undesired interference. In this study, we presented an integrated biosensing nanodevice, termed TRI-HCR, in which hybridization chain reaction (HCR) probes were precisely organized on a triangular DNA origami nanostructure (TRI) with finely-tuned distance, quantity, and pattern. Compared to traditional HCR in the free form, this nanodevice demonstrated increased reaction rate and signal level. We further employed the optimized TRI-HCR for in vivo imaging of a nucleic acid biomarker of inflammatory diseases. In both acute gouty arthritis (AGA) and sepsis-associated acute kidney injury (SA-AKI) model mice, TRI-HCR was capable of diagnosing inflammation in the early stages, significantly earlier than histological examination. We anticipate that this precise spatial preorganization strategy for HCR holds promise for broader applications in early disease detection and monitoring.
生物系统利用精确的空间组织来促进和调节信号网络内的信息传递。受此启发，能够实现精细空间排列的人工支架对于提高反应物的局部浓度、加速特定相互作用以及减少不必要的干扰是很有必要的。在本研究中，我们展示了一种集成生物传感纳米器件，称为TRI-HCR，其中杂交链式反应（HCR）探针以精确调整的距离、数量和模式精确排列在三角形DNA折纸纳米结构（TRI）上。与传统的游离形式HCR相比，这种纳米器件表现出更高的反应速率和信号水平。我们进一步将优化后的TRI-HCR用于炎症性疾病核酸生物标志物的体内成像。在急性痛风性关节炎（AGA）和脓毒症相关性急性肾损伤（SA-AKI）模型小鼠中，TRI-HCR能够在早期阶段诊断炎症，比组织学检查要早得多。我们预计，这种针对HCR的精确空间预组织策略在早期疾病检测和监测方面具有更广泛应用的潜力。
