Sensing of circulating cancer biomarkers with metal nanoparticles

The analysis of circulating cancer biomarkers, including cell-free and circulating tumor DNA, circulating tumor cells, microRNA and exosomes, holds promise in revolutionizing cancer diagnosis and prognosis using body fluid analysis, also known as liquid biopsy. To enable clinical application of these biomarkers, new analytical tools capable of detecting them in very low concentrations in complex sample matrixes are needed. Metal nanoparticles have emerged as extraordinary analytical scaffolds because of their unique optoelectronic properties and ease of functionalization. Hence, multiple analytical techniques have been developed based on these nanoparticles and their plasmonic properties. The aim of this review is to summarize and discuss the present development on the use of metal nanoparticles for the analysis of circulating cancer biomarkers. We examine how metal nanoparticles can be used as (1) analytical transducers in various sensing principles, such as aggregation induced colorimetric assays, plasmon resonance energy transfer, surface enhanced Raman spectroscopy, and refractive index sensing, and (2) signal amplification elements in surface plasmon resonance spectroscopy and electrochemical detection. We critically discuss the clinical relevance of each category of circulating biomarkers, followed by a thorough analysis of how these nanoparticle-based designs have overcome some of the main challenges that gold standard analytical techniques currently face, and what new directions the field may take in the future.