Introduction:
Photodynamic therapy (PDT) is based on the photochemical activation of a photosensitizer to generate reactive oxygen species (ROS) that induce cell death. Hypericin is a natural photosensitizer, but its clinical utility is restricted by poor solubility and limited intracellular accumulation. Liposomal encapsulation improves its stability, delivery, and phototoxic performance. This study evaluates cellular uptake, photocytotoxicity, and migration inhibitory effect following PDT using a liposomal hypericin formulation in breast cancer models.
Methods:
Liposomal hypericin was prepared by the thin-film hydration method. Breast cancer cell lines MCF-7 and MDA-MB-231 cells were incubated with free or liposomal hypericin, and cellular uptake was quantified by flow cytometry based on intrinsic hypericin fluorescence. PDT was performed using orange-light irradiation, followed by assessment of cell viability using the MTT assay. The effect of PDT on cancer cell migration was examined with a wound healing assay by observing scratch closure over time.
Results:
Flow cytometry showed time-dependent changes in intracellular hypericin uptake in both cell lines. Despite the lower fluorescence intensity of liposomal hypericin compared to the free compound, the liposomal formulation produced effective and reproducible light-dependent cytotoxicity with minimal dark toxicity, demonstrating high phototoxicity and low toxicity in the absence of light. PDT with liposomal hypericin also significantly reduced cancer cell migration, reflecting ROS-mediated effects.
Conclusions:
Liposomal encapsulation enhances the photochemical safety and therapeutic applicability of hypericin by enabling controlled delivery and effective PDT responses. These findings support liposomal hypericin as a promising photosensitizer with improved translational potential for photodynamic cancer therapy.