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

作者：Yingcong Zhang, Fanyu Meng, Zhengying Gu, Yiran Deng, Tianbao Liu, Haixia Jiang, Tianxiang Chen, Lin Huang, Jiayi Wang · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-65075-6 · 被引用次数：4 · 研究领域：Advanced biosensing and bioanalysis techniques、Biosensors and Analytical Detection、Nanoplatforms for cancer theranostics

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. Accurately predicting immunotherapy efficacy remains challenging. Here, the authors report a multiplexed blood-based assay using self-assembled, dual-target responsive DNA hydrogels for detection of soluble programmed death-ligand 1 and lactate dehydrogenase which can be used as a tool to help evaluate and predict immunotherapy response.