A Lanthanide-Doped Nanoparticle System for Dual Photodynamic Therapy of Lung Cancer

Lanthanide-doped nanoparticles (NPs) have been used to improve photodynamic therapy (PDT) through modulation of the excitation wavelength using near-infrared (NIR) light or X-rays to achieve upconversion or radioluminescence, respectively. We developed a NP that can undergo both mechanisms to excite a powerful photosensitizer, Rose Bengal (RB), when simultaneously irradiated with NIR and X-rays. A range of ion concentrations were investigated leading to the development of the optimal composition: NaLuF4: 20% Gd3+, 1% Dy3+, 1% Yb3+, 0.001% Er3+. The mechanisms of ion interactions were investigated along with their luminescence properties under both modes of excitation. RB was loaded into a mesoporous silica shell coating the NPs, and studies were completed in vitro to determine the outcome of the treatment on A549 cells. Viability assays, clonogenic assays, and microscopy were used to investigate this system under various conditions and irradiation combinations. Herein, we demonstrate that the NPs without RB act as radiosensitizers when excited with X-rays, enhancing the treatment via a dose enhancement effect. When RB-loaded NPs are excited with NIR and X-rays simultaneously, the dual Photodynamic therapy (PDT) treatment showed the greatest treatment outcome when compared to upconversion PDT and X-ray mediated PDT (X-PDT) individually. This work is a proof of concept that suggests that a dual PDT nanoparticle system could improve the outlook for lung cancer patients in the future