In recent years, photodynamic therapy (PDT) has emerged as an important component of comprehensive cancer treatment owing to its minimally invasive nature, low systemic toxicity, and high selectivity. However, the clinical efficacy of conventional photosensitizers has long been limited by their dependence on oxygen, insufficient tissue penetration, and inadequate targeting precision. Recently, a research team from China Three Gorges University published a review article in the journal BM, systematically summarizing the latest advances in six major classes of organic photosensitizers for cancer PDT: porphyrins, chlorins, phthalocyanines, fused-ring quinones, phenothiazines, and BODIPY derivatives. The review highlights that molecular-structure engineering, the development of nanodelivery systems, and multimodal combination-treatment strategies can substantially enhance reactive oxygen species generation and tumor-killing efficacy. These findings provide a systematic reference for the design of next-generation phototherapeutic agents that are highly efficient, minimally toxic, and suitable for treating deep-seated tumors.
Cancer has long posed a serious threat to human health, and the development of effective and safe therapeutic approaches remains a major focus of medical research. In recent years, photodynamic therapy (PDT) has attracted considerable attention as an emerging minimally invasive treatment modality because of its high selectivity, low toxicity, and suitability for repeated administration. Photosensitizers are the key therapeutic agents responsible for the efficacy of PDT. Compared with conventional inorganic photosensitizers, organic photosensitizers offer greater potential for clinical application owing to their precisely tunable molecular structures, favorable biocompatibility, and relatively rapid metabolic clearance in vivo. Nevertheless, their clinical translation continues to be hindered by several major limitations, including oxygen dependence, insufficient tissue penetration, and inadequate tumor-targeting specificity.
To address these challenges, a research team from China Three Gorges University conducted a systematic review of recent advances in the application of organic photosensitizers to cancer PDT. The researchers classified the major organic photosensitizers currently in use into six categories: porphyrins, chlorins, phthalocyanines, fused-ring quinones, phenothiazines, and BODIPY derivatives. They also comprehensively analyzed the molecular design strategies, approaches for regulating photophysical properties, and nanodelivery systems developed for each class of photosensitizer.
The review shows that molecular-structure optimization and nanoscale engineering can significantly improve the water solubility, tumor accumulation, and cellular uptake of organic photosensitizers. In particular, photosensitizers operating through a Type I photodynamic mechanism can continuously generate reactive oxygen species through electron-transfer pathways under hypoxic conditions, thereby overcoming the strong oxygen dependence of conventional Type II photosensitizers. Meanwhile, second near-infrared-window (NIR-II) absorption and two-photon excitation technologies can extend the effective tissue penetration depth of photosensitizers to the centimeter scale, making phototherapy for deep-seated tumors increasingly feasible. Aggregation-induced emission materials can also retain efficient photosensitizing activity after nanoscale assembly, opening new avenues for precision imaging-guided therapy.
Notably, combining PDT with chemotherapy, photothermal therapy, immunotherapy, and other treatment modalities can produce synergistic therapeutic effects. Such combination strategies not only eradicate tumors locally but also activate systemic antitumor immune responses. Smart nanodelivery systems that respond selectively to features of the tumor microenvironment, such as pH, glutathione levels, and enzyme activity, are emerging as an important means of improving therapeutic specificity while reducing adverse effects.
Despite these promising developments, the research team noted that numerous challenges remain. Most current strategies have been evaluated only in subcutaneous xenograft models, and standardized comparative studies against clinically approved photosensitizers remain insufficient. NIR-II and two-photon technologies also rely on expensive equipment, resulting in relatively high costs for clinical translation. In addition, the selectivity and safety of stimuli-responsive systems in complex physiological environments require further systematic validation.
Dr. Peng Geng summarized the findings as follows: “Continued innovation in organic photosensitizers is bringing new hope to cancer photodynamic therapy. Future research should strengthen pharmacokinetic and toxicological evaluations of novel photosensitizers in large-animal models, promote the establishment of standardized assessment systems, and further investigate the synergistic mechanisms between photodynamic therapy and immunotherapy. These efforts will help accelerate the transition from laboratory research to clinical practice and provide cancer patients with more precise, safe, and effective treatment options.”
The paper, entitled “Recent advances in organic photosensitizers for tumor photodynamic therapy,” was published in Biofunctional Materials (ISSN: 2959-0582). Biofunctional Materials is an online, multidisciplinary, open-access journal that provides a peer-reviewed platform for innovation, research, and development in bioactive materials, biomedical materials, bioinspired materials, biomanufacturing, and other areas related to biofunctional materials.
Citation : Jin Q, Huang Y, Wang W, Lan H, Xiao S, et al. Recent advances in organic photosensitizers for tumor photodynamic therapy. Biofunct. Mater . 2026(2):0006, https://doi.org/10.55092/bm20260006
Biofunctional Materials
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Recent advances in organic photosensitizers for tumor photodynamic therapy
17-Jul-2026