A Comprehensive Review on Recent Developments in Near-Infrared Organic Fluorophores for Breast Cancer: From Molecular Design to Diagnostic Applications

Abstract

Breast cancer is one of the leading causes of cancer-related death of women globally due to its genomic diversity and rapid metastasis. Because of their invasiveness, limited resolution, and patient variability, traditional diagnostic procedures like biopsies and mammography underscore the need for non-invasive, real-time imaging methods. Advancements in the near-infrared (NIR) spectral range (650-1700 nm) have greatly improved early detection, image-guided surgery, and targeted treatment for breast cancer. This is particularly true for fluorescent probes that can be activated by tumor-specific biomarkers such as esterase, cathepsins, and reactive oxygen species (ROS). This article summarizes the design and biomedical applications of organic small-molecule near-infrared fluorophores, including BODIPY, cyanine, squaraine, rhodamine, phenyl, xanthene, and phenothiazine/phenoxazine derivatives. Highly photostable, molecularly tunable, and biomarker specific, these probes "turn on" their fluorescence only in response to signals indicative of disease. In order to more accurately target malignant breast tissue and not benign cells, scientists have created dual-activated probes that react to oxidative stress and enzymatic activity. Furthermore, xanthene, phenyl, rhodamine, and phenoxazine scaffolds are being used more frequently in photodynamic therapy (PDT) and multimodal imaging systems because of their tunable optical properties. The combined efforts of these innovations to overcome challenges, such as tissue autofluorescence and shallow imaging, have improved tumor localization accuracy and treatment success. The study concludes by exploring possible future methods to enhance probes via structural alteration, dual-modal design, and receptor-mediated targeting, before diving into the remaining obstacles including phototoxicity, off-target activation, and fast systemic clearance.