Study of a novel vehicle developed for enhancing the efficacy of radiation therapy

Recently, photodynamic therapy (PDT) has attracted considerable attention as a less invasive method for cancer treatment involving the use of ultraviolet-visible (UV-Vis) light, near-infrared (NIR) light, or X-ray (XR) to activate photosensitizers (PSs) and kill tumor cells. However, the penetration depths of UV-Vis and NIR are not sufficient to reach tumors located in the internal organs. Using XR as a light source requires high doses of protoporphyrin IX (PpIX) and XR irradiation. Therefore, we developed a novel strategy involving the use of low dose XR, therapeutic ultrasound (US) and a newly proposed nanovehicle (SiO2 nanospheres conjugated with PpIX and then decorated with Au nanoparticles; PpIX-loaded Au@SNs). This vehicle was designed for enhancing targeted sonosensitization (i.e., US-induced PpIX sensitization) and exerting a radiation dose enhancement effect. The targeted sonosensitization was enhanced through the PpIX-SiO2 conjugation (which reduces self-quenching of PpIX) and PpIX-mitochondrial colocalization. This synergistically working with the radiation dose enhancement effect of Au and Si might significantly enhance the efficacy of subsequent XR irradiation. Results showed that PpIX-loaded Au@SNs-internalized tumor cells were effectively killed after the sequential administration of US and XR. Importantly, the doses of XR and PpIX are significantly lower than those described in the literature.