Photodynamic efficacy of photosensitizers under an attenuated light dose via lipid nano-carrier-mediated nuclear targeting

Photodynamic therapy (PDT) has emerged as a treatment for certain malignant-like skin, head and neck, gastrointestinal, and gynecological cancers. The broader acceptance of PDT treatment for large or deep-seated tumors is still hindered, at least in part, by the low photodynamic efficiency of photosensitizers (PS) in the deep-seated tumor environment where the light energy fluency rate is severely attenuated after propagation via skin and/or tissue barriers. In this report, efficient nuclear-targeted intracellular delivery of PS is achieved using an easily fabricated yet entirely biocompatible and inexpensive polysaccharide-functionalized nanoscale lipid carrier, which triggers the intracellular release of photosensitizers inside cancer cells and targets cell nuclear to achieve a significantly enhanced photocytotoxicity. Cancer cells are killed efficiently even under an extremely low light fluency of 1 mW/cm2 attenuated via an interval meat layer with a thickness of 3 mm. Therefore, this nuclei-targeting system may contribute to the development of a new generation of PS carriers that fight against deep-seated tumors and that exhibit excellent photodynamic efficiency under faint light irradiation.