Enhanced efficiency of photodynamic therapy-mediated the plant pigment hypericin through Folate-PEG functionalized chitosan nanoparticles

Hypericin (Hy), an anthraquinone-derived pigment, has recently attracted attention as a safe and natural photosensitizer for photodynamic therapy (PDT). However, its clinical applications have been limited by its hydrophobicity and off-target photoactivity. This work aimed to enhance efficacy of Hy-based PDT using a highefficiency and high-specificity vehicle for targeted delivery Hy to the cancer cells. Hy-loaded chitosan nanoparticles (Hy-CNs) were prepared using the ionic gelation technique, and further functionalized with folic acid (FA) and PEG. These generated nanoparticles (PEG-FA-Hy-CNs) were physicochemically characterized using, FTIR spectroscopy, UV-Vis spectroscopy, dynamic light scattering, and SEM analysis and then compared with other Hy formulations in terms the singlet oxygen production, intra cellular uptake, and phototoxicity under suitable irradiation (590 nm, 10 Jcm(-2)). All the formed nanostructures presented a mean particle size about 200-300 nm and greater than 80 % entrapment efficiency. Drug release data of PEG-FA-Hy-CNs indicated a sustained release of Hy and a good correlation with Higuchi model. PEG-FA-Hy-CNs induced a much higher singlet oxygen formation, cellular uptake, photoactivity, and apoptosis compared to Hy-CN, Hy-FA, Hy-PEG, and free Hy. Additionally, these effects were much higher in FA receptors over-expressing breast cancer cells than healthy cell lines. Results suggest that PEG-FA-Hy-CNs can be used for controlled Hy release and active targeting of breast cancer cells, which are beneficial for Hy-based PDT.