Advances in porphyrin-based photosensitizers for photodynamic therapy of A549 lung cancer

Porphyrin-based photosensitizers are widely used in photodynamic therapy (PDT) for A549 lung cancer. However, their clinical efficacy is limited by poor water solubility, the trade-off between fluorescence emission and singlet oxygen generation, and insufficient tumor targeting. To address these issues, researchers have turned to molecular design strategies. By constructing donor-acceptor systems and employing supramolecular assembly, they have significantly improved the photophysical properties of these photosensitizers. Building on these advances, smart delivery systems responsive to multiple tumor-specific stimuli, such as overexpressed matrix metalloproteinases, hypoxia, and acidic pH in the A549 tumor microenvironment, have been developed. These systems enable precise targeting and on-demand activation of the photosensitizer. To overcome the limitations of monotherapy, recent studies combine PDT with chemotherapy, starvation therapy, or ferroptosis. Such combinations enhance cancer cell killing through cascade amplification or mutual reinforcement mechanisms. In parallel, innovative delivery platforms, including engineered probiotics, cell membrane-derived vesicles, and all-API (active pharmaceutical ingredient) nanoparticles, have greatly improved tumor accumulation and biocompatibility of porphyrin photosensitizers. This review systematically integrates these recent advances, providing a solid foundation for the clinical translation of porphyrin-based photosensitizers in precision PDT for A549 lung cancer.