Copper iodine cluster nanoparticles for tumor-targeted X-ray-induced photodynamic therapy

The weakness of visible and near-infrared light penetration depth limits the application of photodynamic therapy (PDT) in deep-seated tumors. Based on the high penetrability of X-rays, X-ray-induced PDT (X-PDT) is a promising new method for treating deep-seated tumors. However, it requires the development of suitable X-ray-induced sensitizers that could employ X-ray energy to produce reactive oxygen species (ROS) efficiently. In this study, a novel X-ray-induced sensitizer (NanoSRF) was developed through a microemulsion method, in which copper iodine cluster compound Cu₂I₂(tpp)₂(2,5-dm-pz) (CIP) and rose bengal (RB) worked as scintillator and photosensitizer, respectively. CIP was synthesized by a simple mechanical grinding method, and subsequently folic acid (FA)-modified albumin was introduced to enable its alliance with RB. NanoSRF exhibited excellent dispersion stability and generated a large amount of ROS under X-ray irradiation. The results of in vitro studies demonstrated its high selectivity for FA receptor-positive cancer cells. Following systemic administration, NanoSRF accumulated in H22 tumors of xenograft-bearing mice, and X-ray irradiation (5.46 Gy) induced a significant inhibition rate of 96.7% in tumor growth. This study pioneers the use of copper iodide cluster as a scintillator in X-PDT, presenting new possibilities for designing scintillators with exceptional X-ray absorption and efficient X-PDT capabilities.