Emerging Nanotechnologies for Liquid Biopsy: The Detection of Circulating Tumor Cells and Extracellular Vesicles

Abstract

Liquid biopsy enables noninvasive and dynamic analysis of molecular or cellular biomarkers, and therefore holds great potential for the diagnosis, prognosis, monitoring of disease progress and treatment efficacy, understanding of disease mechanisms, and identification of therapeutic targets for drug development. In this review, the recent progress in nanomaterials, nanostructures, nanodevices, and nanosensors for liquid biopsy is summarized, with a focus on the detection and molecular characterization of circulating tumor cells (CTCs) and extracellular vesicles (EVs). The developments and advances of nanomaterials and nanostructures in enhancing the sensitivity, specificity, and purity for the detection of CTCs and EVs are discussed. Sensing techniques for signal transduction and amplification as well as visualization strategies are also discussed. New technologies for the reversible release of the isolated CTCs and EVs and for single‐CTC/EV analysis are summarized. Emerging microfluidic platforms for the integral on‐chip isolation, detection, and molecular analysis are also included. The opportunities, challenges, and prospects of these innovative materials and technologies, especially with regard to their feasibility in clinical applications, are discussed. The applications of nanotechnology‐based liquid biopsy will bring new insight into the clinical practice in monitoring and treatment of tumor and other significant diseases.

Human Platelet Membrane Functionalized Microchips with Plasmonic Codes for Cancer Detection

“…Cancer cell‐derived circulating extracellular vesicles (EVs), a key target of “liquid biopsies,” have attracted considerable attention due to their ability to mediate intercellular signaling and their utility for the discovery of novel cancer biomarkers . However, the widespread application of conventional biosensors recognizing cancer threats based on the single ligand‐receptor binding is hindered by the minute amounts of cancer cell‐derived EVs in real clinical samples and the heterogeneity of EV surface markers .…”

Role of extracellular vesicles in tumour microenvironment

“…Analysis of EVs is a promising potential new star in the field of liquid biopsy, and an approach that has attracted more and more attention in recent years is single-EV analysis, which is of crucial significance for the precise analysis and diagnosis of diseases [246]. A multiplexed fluorescent imaging system has been introduced by Lee and colleagues for the detection and analysis of multiplex markers on a single EV, and this technology can analyse up to 11 different markers [247].…”

“…Liquid biopsy is based on the detection and analysis of biomarkers (for instance, circulating tumour cells (CTCs), cell-free nucleic acids (cfNAs), and EVs) in readily-available body fluids such as peripheral blood [ 244 – 246 ]. The first step of major liquid biopsy approaches is isolation and enrichment of targets [ 246 ], and it is important to establish a reliable system.…”

Circulating Tumor Cell Detection in Lung Cancer: But to What End?

“…A number of recent publications and developments within this domain testify to the increasing importance of LB. These studies concern not only fundamental translational and clinical research, but also technological advances [3,4,5,6,7]. They have provided a better understanding of the molecular and cellular mechanisms, the progression of lung cancer, and the treatment of patients.…”