Small organic molecule-based next-generation NIR fluorescent probes for cancer theranostics

Small organic molecule-based near-infrared (NIR) fluorescent probes have emerged as highly promising platforms for cancer phototheranostics, particularly through their integration with photodynamic therapy (PDT). These probes possess several advantageous features, including tunable molecular structures, strong NIR absorption and emission properties, and the capacity for multifunctional integration in both diagnostic and therapeutic contexts. This review provides a comprehensive overview of recent progress in the design and application of NIR fluorescent probes or activatable photosensitizers (PSs), with a specific focus on small organic molecules for PDT. Foundational principles are introduced, including molecular design strategies aimed at enhancing intersystem crossing, optimizing fluorescence emission, and enabling selective activation under tumor-specific conditions. The main discussion centers on the correlation between photophysical properties, structural characteristics, and overall diagnostic and therapeutic efficacy. Emphasis is placed on emerging approaches involving synergistic and precision therapies, PS capable of Type I ROS generation, NIR-II emission, and the development of self-assembled nanostructured probes. The review concludes with a critical discussion of current challenges and prospective directions for advancing the application of small organic molecule-based NIR fluorescent probes in cancer photodynamic theranostics.