Nanotechnology-enhanced liquid biopsies and genomic biomarkers: Emerging landscapes for early cancer detection

Early detection of cancer is essential for improving patient survival, yet current diagnostic methods such as imaging and tissue biopsy are limited by invasiveness, sampling bias and low sensitivity at early disease stages. Liquid biopsy has emerged as a minimally invasive approach that enables dynamic analysis of circulating tumor-derived components, including circulating tumor DNA (ctDNA), exosomes and circulating tumor cells (CTCs). Genomic and epigenomic biomarkers such as somatic mutations, copy number variations, DNA methylation patterns and transcriptomic signatures are recognized as informative indicators of tumor initiation and progression. However, their clinical implementation is constrained by the extremely low abundance of these analytes in circulation and the technical limitations of conventional detection platforms. Nanotechnology addresses these challenges by enabling highly sensitive, selective and multiplex detection of rare biomarkers. Nanoparticles, nanostructured sensors and nanoscale enrichment platforms support single-molecule detection of ctDNA, micro RNA and methylation signatures while minimizing background interference. Integration of these platforms with next-generation sequencing and machine learning has led to the emergence of nano genomic profiling, which enables early, accurate and personalized cancer detection. This review summarizes recent advances at the intersection of nanotechnology, liquid biopsy and gene-based biomarker discovery, highlights key strategies for biomarker capture and signal amplification, examines challenges related to standardization and clinical translation and outlines future directions toward multi-analyte, point-of-care diagnostic platforms capable of transforming early cancer detection.