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Journal of Translational Medicine (2026) 24:865  \n[https://doi.org/10.1186/s12967-026-08240-9](https://doi.org/10.1186/s12967-026-08240-9)  \nJournal of Translational Medicine  \nREVIEW Open Access  \nAdvances in near-infrared fluorescent probes for the tumor microenvironment  \nHaodong Hu1,2, Changyue Zhang1,2, Xiaoqi Kong1,2, Ye Chen1,3 and Ruijiao Chen1,2,3,4*  \nAbstract  \nBackground Cancer remains a major threat to human health worldwide, but with progress in early diagnosis and treatment technology, the progression of cancer has been effectively slowed. Near-infrared (NIR) fluorescent probes are noninvasive imaging tools that show great promise for early tumor detection and intra-operative guidance due to their high sensitivity, deep tissue penetration, and high signal-to-noise ratio.  \nMain body In recent years, the rapid development of NIR fluorescent probes has been driven by a growing understanding of the unique characteristics of the tumor microenvironment. Targeting these features, such as pH, viscosity, polarity, hypoxia, and enzymes, has become a key strategy in the rational design of sensitive small-molecule fluorescent probes for cancer diagnosis and therapy. In this review, we have summarized the recent progress in  \nNIR fluorescent probes for the tumor microenvironment, with an emphasis on their design principles, imaging performance, potential applications, and the challenges faced in clinical translation.  \nConclusions Despite certain progress in near-infrared fluorescent probes, challenges remain, such as tumor heterogeneity and clinical translation. Future efforts should focus on multi-responsive designs, improved photostability, and multimodal imaging strategies. We hope this review can provide a valuable reference for the development of novel fluorescent probes.  \nKeywords Tumor microenvironment, Cancer marker, NIR fluorescent probe  \nIntroduction  \nCancer is a major disease that poses a serious threat to human life and health. It is mainly attributed to population growth and ageing [1], increasing environmental pollution [2, 3], and unhealthy living habits (smoking, sleep deprivation, and physical inactivity) [4]. The  \n*Correspondence:  \nRuijiao Chen  \n[chenrj@mail.jnmc.edu.cn](chenrj@mail.jnmc.edu.cn)  \n1College of Medical Imaging and Laboratory, Jining Medical University, Jining 272067, China  \n2School of Pharmacy, Binzhou Medical University, Yantai 264003, China 3School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China  \n4Affiliated Jinan Third People’s Hospital of Jining Medical University, Jining Medical University, Jinan 250132, China  \ncombination of these factors has led to a continuous increase in the incidence of tumors. According to the latest data from the International Agency for Research on Cancer, in 2020, approximately 20 million new cancer cases and about 9.7 million cancer-related deaths were reported [5]. Therefore, the early detection and diagnosis of cancer are essential to reduce cancer mortality. In the early stages of tumor development and progression, cells undergo a variety of changes, making them different from normal cells. These changes include the abnormal expression of certain proteins [6], enzymes [7], and oxidation–reduction substances [8], as well as alterationsin physiological parameters such as viscosity, polarity, and pH [9]. The above distinctions between tumors and  \n© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other","cbCaiayiB2tyru8C","https://ap.wps.com/l/cbCaiayiB2tyru8C","pdf",4354980,23,"English","# Abstract\n# Main body\n## Tumor microenvironment targets and probe design\n## Imaging performance and clinical translation challenges\n# Conclusions\n# Keywords\n# Introduction\n## Cancer burden and need for early diagnosis\n## Tumor cell changes and microenvironment hallmarks\n## Imaging modalities and limitations","[{\"question\":\"Why are near-infrared fluorescent probes useful for cancer detection and guidance?\",\"answer\":\"They enable noninvasive imaging with high sensitivity, deep tissue penetration, and a strong signal-to-noise ratio, supporting early detection and intra-operative guidance.\"},{\"question\":\"What tumor microenvironment features are commonly targeted in NIR fluorescent probe design?\",\"answer\":\"Key targets include pH, viscosity, polarity, hypoxia, and enzymes, which reflect distinctive conditions in the tumor microenvironment.\"},{\"question\":\"What challenges remain before NIR fluorescent probes can be widely used clinically?\",\"answer\":\"Tumor heterogeneity and clinical translation difficulties persist, and future work should emphasize multi-responsive designs, improved photostability, and multimodal imaging strategies.\"}]","Advances in near-infrared fluorescent probes for the tumor microenvironment - Review | PDF",1790110728,58]