Nanotechnology-Assisted Molecular Profiling: Emerging Advances in Circulating Tumor DNA Detection

Jiayi Kang,1– 3,* Xing Ke,3,* Yanan Zhao,1 Yunlan Zhou1,3 1College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2DNA Molecular Materials and Biomedical Laboratory, Institute of Molecular Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Clinical Laboratory, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yunlan Zhou, Email [email protected] Yanan Zhao, Email [email protected]: Tumor-derived circulating cell-free DNA (ctDNA) has emerged as a pivotal biomarker for non-invasive cancer diagnosis, treatment monitoring, and prognostic evaluation. However, its inherently low abundance, high fragmentation, and rapid degradation impose stringent requirements on assay sensitivity, specificity, and analytical robustness. Rapid advances in nanotechnology have significantly accelerated progress in ctDNA detection. This review summarizes recent nanotechnology-assisted strategies for ctDNA analysis, including surface-engineered nanomaterials for selective enrichment, nano-enabled signal amplification modalities, and integrated platforms such as CRISPR-based detection, microfluidics and nanopore technologies. We further highlight nanostructure-based approaches for decoding methylation, fragmentation profiles, and multi-omics signatures, focusing on their potential to enhance early cancer detection and real-time therapeutic assessment. Moreover, increasing incorporation of artificial intelligence (AI) which spans nanostructure characterization, aptamer and probe design, multi-omics data integration, and algorithm development is reshaping the landscape of nano-assisted liquid biopsy. Finally, current challenges and future perspectives concerning the clinical translation of nanotechnology-assisted ctDNA detection are presented, emphasizing standardization, biocompatibility, automation, and regulatory readiness. Overall, this review provides a comprehensive outlook on how converging nanotechnology and AI innovations are advancing ctDNA-based precision oncology.Keywords: nanomaterials, circulating tumor DNA, multi-omics, machine learning, cancer diagnostics