Citation: Liuyan Zhou, Luyin Wang, Xiaolu Li, Meiling Ren, Shengqiang Hu, Mengjiao Huang, Shulin Zhao, Liangliang Zhang. Construction of tri-input DNA circuits via a double-blocking strategy for spatiotemporally precise in vivo fluorescence imaging[J]. Chinese Chemical Letters, ;2026, 37(10): 112234. doi: 10.1016/j.cclet.2025.112234 shu

Construction of tri-input DNA circuits via a double-blocking strategy for spatiotemporally precise in vivo fluorescence imaging

Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Guangxi Key Laboratory of Chemistry and Molecular Engineering of Medicinal Resources, University Engineering Research Center for Chemistry of Characteristic Medicinal Resources (Guangxi), School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China

zn_sqhu@163.com

liangzhang319@163.com

Received Date: 14 September 2025
Revised Date: 29 November 2025
Accepted Date: 8 December 2025
Available Online: 10 December 2025

Figures(5)

Owing to their sophisticated information-processing capabilities, multi-input DNA circuits (DCs) show great potential in spatiotemporally precise in vivo imaging of diseases. Nevertheless, engineering simple yet versatile multi-input DCs remain a big challenge. Herein, tri-input DNA circuits (tiDCs) based on a DNAzyme-driven walker system were developed via a novel double-blocking strategy, enabling high spatiotemporal-precision fluorescence imaging in vivo. A hairpin structure containing photocleavable linker was designed as the first blocking unit to lock the miRNA-complementary strand, while the miRNA-complementary strand was introduced as the second blocking unit to inhibit the Zn²⁺-specific DNAzyme-contained walker strand. By leveraging upconversion nanoparticles for targeted delivery and light transduction, the tiDCs generated amplified fluorescence signals exclusively upon simultaneous inputs of near-infrared (NIR) light, miRNA, and Zn²⁺, achieving spatiotemporally controlled imaging of arthritis. This work establishes a programmable molecular platform for visualizing complex biological systems in vivo, offering new pathways to advance diagnostic precision and therapeutic outcomes.
- Tri-input DNA circuits,
- DNAzyme-based walking system,
- Upconversion nanoparticles,
- Spatiotemporal control,
- Fluorescence imaging
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