Molecular Engineering of Porphyrins for Near-Infrared Bioimaging and Phototherapy

Porphyrins represent fundamental molecules in phototherapy, with their derivatives clinically approved as photosensitizers for photodynamic therapy (PDT). Their applications have expanded from traditional fluorescence imaging and PDT to diverse approaches, including photoacoustic imaging and photothermal therapy. Compared with visible light, near-infrared (NIR) light offers enhanced safety and efficiency in phototheranostics due to its greater tissue penetration depth. However, conventional porphyrins lack NIR absorption; furthermore, they suffer from aggregation-caused quenching and limited photostability. This review systematically summarizes recent advances in addressing these problems through molecular design of porphyrins, employing ligand π-system engineering, metal coordination, and nanoassembly to achieve precise control over their photophysical properties. We focus on achieving bathochromic shifts with enhanced intensity in absorption/emission spectra in porphyrins and on regulating energy conversion pathways to selectively improve NIR luminescence, reactive oxygen species generation, or photothermal conversion. These advances facilitate the development of highly efficient and controllable NIR-activatable agents, highlighting the promising role of porphyrin-based materials and paving the way for their clinical translation in precision multifunctional phototheranostics.