Cancer, characterized by abnormal cell proliferation, is one of the most important chronic and complex diseases. Not only is it a serious threat to people’s health and life, but also it has been a leading cause of death in every country in the world for a long time. It has caused huge loss to society, including the negative influence on the emotions and economies of patients and their families, the burden on medical resources and treatment investments, and the loss of human resources. The cancer survival rate is usually low, which may be related to a lack of timely and effective detection, which leads to late diagnosis and missed opportunities for targeted and standardized treatment. Early detection and effective diagnosis of cancer can significantly reduce the death rates of patients through early and effective prevention and treatment.
Tumor markers are defined as substances that are synthesized and released by tumor cells themselves or that are produced by the body in response to the development and proliferation of tumors, and which can be identified in blood, urine, saliva, tissue, and other body fluids. Detection of tumor markers is an important indicator for cancer diagnosis, treatment, and efficient monitoring. It complements other clinical examination methods, such as imaging, endoscopic, and pathological examinations. The early detection of tumor markers has the advantages of being minimally or noninvasive, rapid, and convenient, and it has great application potential in cancer screening, diagnosis, treatment, prognosis, and other aspects.
In the past few decades, advances in the early detection of cancer have led cancer research to a minted stage. Based on the specific recognition of intracellular and extracellular biomarkers, several promising detection methods have been developed, including the polymerase chain reaction, enzyme-linked immunosorbent assay, electrophoresis, surface plasmon resonance, surface-enhanced Raman spectroscopy, electrochemical sensing, mass spectrometry, flow cytometry, and other technologies. However, some of these methods are limited by being expensive, time-consuming, and complicated operate. In most cases, the relatively low sensitivity and accuracy of these methods are not adequate to meet new clinical requirements, and they cannot be used in an environment with few resources and extensive point-of-care detection. It is, therefore, urgent to develop a new detection technology with the characteristics of high efficiency, sensitivity, accuracy, stability, and economic friendliness.
Fluorescence methods have attracted the attention of researchers in recent years because of their advantages of high sensitivity, low cost of instrumentation, and ease of operation, and tremendous advances have been made. The fluorescence method has been widely used for ultrasensitive and rapid detections of tumor markers, and the exploration of this method for the accurate detection of new markers is still being implemented in the laboratory. In addition, it is being used both to improve old methods and to create new methods for detecting tumor markers. Consequently, it is both important and necessary to summarize existing research in order to predict and guide the future development of the fluorescence method for tumor marker detection.
This paper first introduces tumor biomarkers and methods for detecting them and then compares the principles and characteristics of different detection methods (Table 1). Next, novel fluorescent-probe materials—such as carbon dots, upconversion nanoparticles, and polymer dots—are briefly introduced and their applications in the detection of biomarkers are summarized (Table 2). Various methods of capturing and detecting circulating tumor cells (CTCs) are then introduced. Based on traditional methods for enhancing the capture efficiency and detection sensitivity for CTCs, the effective introduction of near-infrared light (Fig. 3) and the one-step method for detecting CTCs has gradually become a new research focus (Fig. 4). Improvements in the traditional polymerase chain reaction for detecting circulating tumor DNA (ctDNA) and the development of fluorescence biosensor technology are next introduced (Fig. 5). Biosensors and emerging diagnostic technologies based on various fluorescent materials have greatly facilitated the development of ctDNA detection. Several methods for the comprehensive detection of exosomes are subsequently introduced (Fig. 6); they mainly include the combined application of microfluidics, nanotechnology, and fluorescent nanomaterials. Finally, the detection of carcinoembryonic antigen, alpha-fetoprotein, prostate-specific antigen, and simultaneous multiple detections of several biomarkers (Fig. 10) are briefly introduced. In addition to the basic requirements of high sensitivity and high specificity, fast, affordable, and portable detection platforms—such as biochips, immunochromatographic test strips, and point-of-care detection devices—are emerging.
In summary, the fluorescence method has a wide range of applications to many diseases, including tumor detection. Although great advancements have already been made, many challenges remain in tumor-marker detection. Detection technology based on the fluorescence method still needs to be explored and improved constantly to provide high detection sensitivity and accuracy, so that it can meet application demands more widely and more simply and adapt to the constantly updated understanding of disease mechanisms and test requirements.
