Progress in the past five years of small organic molecule dyes for tumor microenvironment imaging.

The tumor microenvironment (TME) is the survival environment for tumor cell proliferation and metastasis in deep tissues. Prognostic factors, such as growth, invasion and metastasis of malignant tumors, are closely related to changes in physiological parameters, including hypoxia, enzymes, low extracellular pH, and reduction conditions. Therefore, it is of great clinical significance to study tumor microenvironment markers to evaluate tumor progression and predict therapeutic effects. Organic fluorescent dyes are popular because of their small size, easy modification, adjustable luminescence and simple elucidation of their mechanism, and are widely used in tumor diagnosis and treatment. This paper reviews recent progress in fluorescent probes based on small organic molecules for imaging TME markers. Firstly, the design mechanism of a fluorescent probe is discussed, and then the application of pH, hypoxia, and reactive oxygen species, and a reduction-condition-responsive fluorescent probe in tumor imaging is discussed in detail. Finally, the prospects for the application of small-molecule fluorescent probes for imaging a tumor microenvironment in vivo are explored, but the potential application of small-molecule fluorescent probes in the early diagnosis of cancer as well as in the clinical laboratory for differentiating cancers, and further use in image-guided tumor surgery still face great challenges.