Nano-biosensors for circulating tumor markers: advancing liquid biopsy toward precision cancer diagnostics

Early detection of cancer remains a major challenge in oncology. Circulating tumour markers (CTMs), including circulating tumour cells, circulating tumour DNA, exosomes, microRNAs, and tumour-associated proteins, offer a minimally invasive strategy for monitoring tumour dynamics through liquid biopsy. However, their clinical translation is limited by low abundance, heterogeneity, and instability in body fluids. Recent advances in nanotechnology have enabled the development of highly sensitive and specific nano-biosensors that address many of these barriers. This review highlights the current progress in CTM detection using electrochemical, optical, plasmonic, and microfluidic-integrated platforms. Advanced nanomaterials such as graphene, carbon nanotubes, noble metal nanoparticles, quantum dots, and nanozymes are discussed for their roles in signal amplification, surface functionalization, and biomarker selectivity. Special focus is placed on lab-on-a-chip and wearable biosensors for multi-marker, point-of-care testing. To amplify the signals associated with nanobiosensors, various technologies, such as surface functionalization, aptamer and antibody functionalization, and nanozymes, have been integrated with the nanobiosensors. PurposeCirculating tumour markers (CTMs) offer a minimally invasive approach for early cancer diagnosis and monitoring through liquid biopsy. However, their clinical utility is limited by low abundance, heterogeneity, and instability in biological fluids. Several nanotechnology based approaches are being developed to overcome these limitations. This review summarizes the recent advances in these nanotechnology-based biosensors for CTM detection.MethodsRecent studies on nano-biosensor platforms for CTM detection were reviewed. Electrochemical, optical, plasmonic, and microfluidic-integrated systems were examined, with emphasis on the use of graphene, carbon nanotubes, noble metal nanoparticles, quantum dots, and nanozymes. Signal enhancement strategies, including surface functionalization and aptamer- or antibody-based recognition, were also evaluated.ResultsNanomaterial-enabled biosensors have demonstrated improved sensitivity, specificity, and biomarker selectivity. Advanced nanomaterials enhance signal transduction and amplification, while aptamer and antibody functionalization improves target recognition. Integration with microfluidic technologies has enabled rapid, multiplexed, and point-of-care detection of CTMs. Emerging lab-on-a-chip and wearable biosensors further support real-time monitoring and decentralized testing, highlighting their potential for clinical applications.ConclusionNano-biosensors provide an effective strategy to overcome major challenges associated with CTM detection. The combination of advanced nanomaterials, signal amplification approaches, and portable sensing platforms has significantly improved analytical performance. Continued development of multi-marker, lab-on-a-chip, and wearable biosensors may accelerate the clinical translation of liquid biopsy technologies for early cancer diagnosis, disease monitoring, and personalized treatment.