Tehran University of Medical Sciences Frontiers in Biomedical Technologies 2345-5837 0 0 2026 08 19 1660 1660 Bahareh Khalili Najafabad Department of Biomedical Engineering and Medical physics, Shahid Beheshti university of Medical Sciences, Tehran, Iran. Mehdi Hoseini 2Department of Radiology Technology, School of Paramedical Sciences, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran. Amirhossein Rashnoodi 1Department of Biomedical Engineering and Medical physics, Shahid Beheshti university of Medical Sciences, Tehran, Iran. Saleh Rouhi 4Department of Medical Physics, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran. Soroush Najafisarvestani 5Department of Medical Physics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. Zeynab Seraj 1Department of Biomedical Engineering and Medical physics, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2026 06 23 2026 08 19   Abstract Introduction: Photodynamic therapy (PDT) has attracted considerable attention as a non-invasive and selective method for cancer treatment. In this study, the photodynamic effects of nanomicelles loaded with the dye toluidine blue (TB) were evaluated on human lung cancer (QU-DB) and non-cancerous (MRC-5) cell lines. Nanomicelles, as biocompatible carriers, possess the ability to improve solubility, stability, and targeted accumulation of a photosensitizer (PS), while showing enhanced tumor tissue accumulation through the enhanced permeability and retention (EPR) effect. Methods: The TB-loaded nanomicelles were synthesized using the direct dissolution method and underwent physicochemical characterization. Then, cells were irradiated with laser red light (λ = 655 nm) at doses of 10, 20, and 40 J/cm². Post-irradiation, cell viability was quantified via the MTT assay, enabling the calculation of key therapeutic indices such as IC₅₀, ED₅₀, and the synergy index (SI). Results: The results demonstrated that encapsulating TB in nanomicelles increased optical absorption, reduced dye aggregation, and consequently enhanced reactive oxygen species (ROS) generation efficiency. The photodynamic effect of TB-loaded nanomicelles was significantly stronger in the QU-DB cancer cell line compared with free TB, while inducing lower toxicity in the non-tumor MRC-5 cells. Thus, the selective distinction between tumor and non- cancerous cell lines was confirmed. Furthermore, increasing light dose resulted in greater cytotoxicity, with dose-dependent reductions in cell survival. However, no favorable selectivity index was obtained when comparing micellar drug cytotoxicity with the free PS (p > 0.05). Conclusion: TB-loaded nanomicelles represent a promising drug delivery system to enhance the efficacy and selectivity of PDT in lung cancer while reducing its off-target effects. https://fbt.tums.ac.ir/index.php/fbt/article/view/1660