A class of near-infrared fluorescence (NIRF) heptamethine cyanine dyes that are taken up and accumulated specifically in cancer cells without chemical conjugation have recently emerged as promising tools for tumor imaging and targeting.In addition to their fluorescence and nuclear imaging-based tumor-imaging properties,these dyes can be developed as drug carriers to safely deliver chemotherapy drugs to tumors.The preferential uptake of dyes into cancer but not normal cells is cooperatively mediated by the prevailing activation of a group of organic anion-transporting polypeptides (OATPs) on cancer cell membranes,as well as tumor hypoxia and increased mitochondrial membrane potential in cancer cells.Such mechanistic explorations have greatly advanced the current application and future development of NIRF dyes and their derivatives as novel anticancer theranostic agents.We summarized current knowledge and emerging advances in NIRF dyes,including molecular characterization,multimodal development and uptake mechanisms,and their growing potential for preclinical and clinical use.