Toluidine Blue-Loaded Nanomicelles for Photodynamic Therapy of Lung Cancer: An In-vitro Study

Enhanced Photodynamic Efficacy via Nanomicellar Encapsulation

Abstract

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.