Breakthrough in ultrasensitive cancer detection: peptide-based sensor enables dual biomarker analysis
image: This study introduces a novel signal amplification method induced by aggregation, which achieves specific recognition and sensitive detection of two cancer biomarkers through the rational design of peptide-nucleic acid sequences. Compared to methods that do not amplify signals, this innovative approach significantly reduces the detection limits of biomarkers, minimizes time costs, and enhances overall detection efficiency.
Credit: Nano Research, Tsinghua University Press
With the advancement of molecular diagnostics, multiplex biomarker detection has gained prominence for its enhanced accuracy in cancer diagnosis. A research team led by Prof. Liang Yuan and Lei Liu at Jiangsu University has developed a novel electrochemical biosensor using peptide self-assembly engineering (PSA-e-SA) to achieve ultrasensitive, simultaneous detection of carcinoembryonic antigen (CEA) and microRNA-21 (miR-21)—key cancer biomarkers critical for tumor diagnosis, prognosis, and treatment monitoring. Published in Nano Research (June 5, 2025), this breakthrough addresses a critical challenge: detecting ultra-low biomarker levels during early-stage cancer when symptoms are absent.
Early cancer detection significantly improves survival rates, but existing methods struggle with trace biomarker concentrations and limitations like complex synthesis, instability, and high costs. The PSA-e-SA strategy overcomes these barriers by integrating peptide self-assembly’s unique advantages—superior biocompatibility, programmable molecular recognition, and signal amplification under mild conditions—to enable rapid, cost-effective, and scalable multiplex detection.
Unlike conventional nanomaterials, the biosensor leverages peptides’ innate ability to self-assemble into functional nanostructures (e.g., nanofibers) via non-covalent interactions (hydrogen bonds, hydrophobic effects). The design combines a hydrophobic self-assembly module (C16-Pep) with recognition elements (DNA for miR-21, aptamers for CEA) and electroactive probes (Fc and MB). Strategic modifications—maleimide and thiol groups for crosslinking, hydrophilic spacers for stability—ensure efficient target binding and signal amplification.
“Peptides’ programmable structures and dynamic self-assembly open new avenues for next-generation biosensing,” explained Prof. Yuan, highlighting the platform’s core innovation: merging molecular recognition and signal amplification within a single peptide framework. This not only enables ultrasensitive quantification of biomarkers at the clinically relevant low concentrations typical of early-stage cancer but also outperforms traditional methods dependent on complex material synthesis. The study further demonstrates a versatile framework where modular peptide designs, through strategic sequence modifications, can be adapted to diverse targets (like proteins and RNAs), offering a scalable solution for early cancer diagnostics and personalized therapy monitoring.
The team aims to expand biomarker targets and advance clinical trials. “Our ultimate goal is a universal biosensing toolkit for early diagnosis across diseases,” said Prof. Liu. Potential applications include low-cost point-of-care devices for high-risk population screening and real-time treatment response tracking. This work underscores peptide self-assembly’s transformative role in bridging lab innovation with clinical needs, offering a biocompatible, high-precision platform to revolutionize cancer diagnostics.
Collaborators including Zihao Li and Baole Zhang from School of Materials Science & Engineering at Jiangsu University, together with Taofeng Zhu from the Department of Pulmonary and Critical Care Medicine at Yixing Hospital Affiliated to Jiangsu University, contributed to validating the platform’s robustness.
The authors extend their appreciation to the National Natural Science Foundation of China (NSFC, Grants No. 22004051, 22072060), the Natural Science Foundation of Jiangsu Province (BK20180858), the China Postdoctoral Science Foundation (Grant No. 2019M661733), the Scientific Research Starting Foundation for Senior Talent at Jiangsu University (Grant No. 18JDG025), and Science Foundation of Wuxi Health Committee (No. BJ202220), Top Talent Support Program for young and middle-aged people of Wuxi Health Committee (Grant no. BJ2023105) and Opening of Jiangsu Provincial Key Laboratory of Laboratory Medicine (Grant no. JSKLM-T-2024-1).
About the Authors
Dr. Taofeng Zhu, Associate Chief Physician of Yixing Hospital Affiliated to Jiangsu University, Corresponding Author of this article, Director of the Department of General Medicine at Yixing Hospital Affiliated to Jiangsu University, Third-Level Cultivation Candidate of Jiangsu Province "Three Three Three Project", Top Talent of the Double Hundred Plan of Wuxi Health Commission. His research directions focus on the early diagnosis of diseases using biomarkers and their clinical applications. He has presided over one project funded by the National Natural Science Foundation of China and one project supported by the Jiangsu Provincial Health Commission Fund. So far, he has published more than 10 SCI-indexed papers in renowned journals such as Molecular Cancer, Advanced Science, Journal of Hazardous Materials, Biomaterials Science, and Cell Death & Disease.
Prof. Liang Yuan, Research Fellow at the School of Materials Science and Engineering, Jiangsu University, and Corresponding Author of this article. His main research interests focus on the construction of sensing interfaces with controllable structure design and the development of efficient, highly sensitive analytical detection methods. He has conducted extensive research in the design and modification of functional biomolecular materials (such as peptides and DNA), peptide nanozymes, fabrication of biosensors, and signal amplification strategies for sensing detection.
He has published over 30 papers in internationally renowned academic journals, including Chemical Science, ACS Nano, Analytical Chemistry, NPG Asia Materials, Biosensors and Bioelectronics, Sensors and Actuators B: Chemical, and Chemical Communications. These works have been cited over 1,100 times with an h-index of 18. He has hosted one project from the National Natural Science Foundation of China, one from the Jiangsu Provincial Natural Science Foundation, one from the China Postdoctoral Science Foundation, and an open fund from the State Key Laboratory of Life Analytical Chemistry at Nanjing University. He also participated in (ranked 4th) a National Major Scientific Instrument Development Project.
Prof. Lei Liu, the corresponding author of this study, is a full professor at the School of Materials Science and Engineering, Jiangsu University, where he also serves as the Director of the Institute for Advanced Materials and Deputy Director of the Jiangsu Provincial International Joint Research Laboratory, Jiangsu Distinguished Professor and Jiangsu "Double Innovation" Talent (University Innovation Category). Prof. Liu's research primarily focuses on biomolecular assembly, biofunctional interfaces and their biomedical applications. He has secured three National Natural Science Foundation of China grants, one Jiangsu Provincial Natural Science Foundation project, and two Jiangsu Talent Program research grants. With an impressive publication record of 100 SCI-indexed papers in prestigious journals including Nature Nanotechnology, Angewandte Chemie International Edition, Chemical Science, ACS Nano, Nano Letters, Nano Today, Advanced Science, Analytical Chemistry, Materials Horizons, and so on. His work has been featured six times as journal cover articles, with one paper recognized as an ESI Highly Cited Paper. Prof. Liu holds 20 Chinese invention patents (15 granted) and 1 PCT patent, and has authored a chapter in the Springer monograph Nucleic Acid Nanotechnology. His academic service includes membership on the Standing Committee of the 2017 IEEE 3M-NANO International Conference and the Expert Committee of the China Biochemical Pharmaceutical Association's Polypeptide Branch. His outstanding contributions were acknowledged with the 2019 IFAM International Forum on Advanced Materials "Outstanding Young Scientist Award" conferred by the Chinese Academy of Engineering.
About Nano Research
Nano Research is a peer-reviewed, open access, international and interdisciplinary research journal, sponsored by Tsinghua University and the Chinese Chemical Society, published by Tsinghua University Press on the platform SciOpen. It publishes original high-quality research and significant review articles on all aspects of nanoscience and nanotechnology, ranging from basic aspects of the science of nanoscale materials to practical applications of such materials. After 18 years of development, it has become one of the most influential academic journals in the nano field. Nano Research has published more than 1,000 papers every year from 2022, with its cumulative count surpassing 7,000 articles. In 2024 InCites Journal Citation Reports, its 2024 IF is 9.0 (8.7, 5 years), and it continues to be the Q1 area among the four subject classifications. Nano Research Award, established by Nano Research together with TUP and Springer Nature in 2013, and Nano Research Young Innovators (NR45) Awards, established by Nano Research in 2018, have become international academic awards with global influence.