A multiplexed assay by self-assembled dual-target responsive DNA hydrogels for efficacy evaluation of immunotherapy

Yingcong Zhang, Fanyu Meng, Zhengying Gu, Yiran Deng, Tianbao Liu, Haixia Jiang, Tianxiang Chen (), Lin Huang () and Jiayi Wang ()
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Yingcong Zhang: Shanghai Jiao Tong University School of Medicine, Department of Clinical Laboratory, Shanghai Chest Hospital
Fanyu Meng: Shanghai Jiao Tong University School of Medicine, Department of Clinical Laboratory, Shanghai Chest Hospital
Zhengying Gu: Shanghai Jiao Tong University School of Medicine, Department of Clinical Laboratory, Shanghai Chest Hospital
Yiran Deng: Shanghai Jiao Tong University School of Medicine, Department of Clinical Laboratory, Shanghai Chest Hospital
Tianbao Liu: Shanghai Jiao Tong University School of Medicine, Department of Cardiology, Shanghai Chest Hospital
Haixia Jiang: Shanghai Jiao Tong University School of Medicine, Department of Clinical Laboratory, Shanghai Chest Hospital
Tianxiang Chen: Shanghai Jiao Tong University School of Medicine, Department of Thoracic Surgery, Shanghai Chest Hospital
Lin Huang: Shanghai Jiao Tong University School of Medicine, Department of Clinical Laboratory, Shanghai Chest Hospital
Jiayi Wang: Shanghai Jiao Tong University School of Medicine, Department of Clinical Laboratory, Shanghai Chest Hospital

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Immunotherapy has revolutionized cancer treatment, yet its efficacy is limited to a specific patient subset. This underscores the critical clinical demand for accessible assays capable of assessing immunotherapy outcomes and enabling timely adjustments to personalized medical care. Here, we present a multiplexed assay based on dual-target responsive DNA hydrogels for the simultaneous detection of soluble programmed death-ligand 1 and lactate dehydrogenase in lung cancer patients. The DNA hydrogel, constructed through a self-assembly strategy, achieves superior performance by reducing background noise by 33.8% and improving the signal-to-noise ratio by 61.5%. By integrating rolling circle amplification, the assay enables ultrasensitive detection at femtomolar levels. When further combining additional clinical biomarkers, the assay demonstrates strong predictive ability for immunotherapy response, achieving an area under the curve value of 0.935 in clinical cohort. Collectively, this blood-based assay offers a versatile and effective approach for advancing biomarker-based evaluations of immunotherapy outcomes.

Date: 2025
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DOI: 10.1038/s41467-025-65075-6

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