Recent advances in chemiluminescence probes for Tumor microenvironment with applications in cancer diagnosis and...

Optical imaging enables noninvasive visualization of molecular processes in living systems and plays an essential role in cancer research. Among available optical modalities, chemiluminescence imaging (CLI) offers a distinctive advantage for probing the tumor microenvironment (TME) by eliminating external excitation and minimizing background interference. Because photon emission arises directly from chemical reactions, CLI converts endogenous biochemical activity within the TME into localized and selective optical signals. This review examines recent advances in the design of TME-responsive chemiluminescence (CL) probes for cancer diagnosis and therapy. Despite rapid methodological progress, a persistent knowledge gap remains in quantitatively correlating molecular design with heterogeneous TME characteristics, while simultaneously addressing translational constraints such as tissue penetration, pharmacokinetics, and probe manufacturability. The historical evolution of three major CL scaffolds-luminol, peroxyoxalate, and dioxetane-is first outlined to illustrate how structural innovations have progressively improved biological compatibility and functional specificity. Design strategies targeting representative TME hallmarks, including redox imbalance, hypoxia, acidic pH, and aberrant enzyme activity, are then systematically discussed. By comparing applications across distinct tumor models, including hepatocellular, breast, and lung cancers, this review highlights how tumor-type-specific biochemical heterogeneity fundamentally shapes imaging performance and therapeutic relevance. The review concludes with a perspective on remaining challenges and emerging directions, emphasizing standardization, multifunctional integration, and application-driven probe design to advance CLI toward broader biomedical and translational impact.