Light-assisted Gadofullerene Nanoparticles Disrupt the Tumor Vasculatures for Potent Melanoma Treatment
The traditional photodynamic therapy (PDT) using photosensitizer and oxygen under light generates the reactive oxygen species (ROS) to kill the tumor cells. However, its treatment efficiency is limited by insufficient oxygen in tumor cells. Herein, β-alanine modified gadofullerene nanoparticles (GFNPs) were explored to disrupt tumor vasculatures assisted by light for potent melanoma treatment. As oxygen-rich in tumor vasculature, the yields of photo-induced singlet oxygen (1O2) by GFNPs are not subjected to the hypoxemia of tumor tissues. Different from the small molecule photosensitizer Chlorin e6 (Ce6), GFNPs realize high-efficiency tumor vascular disruption under light observed by the mice tumor vascular dorsal skin fold chamber (DSFC). The tumor vascular disruption efficiency of GFNPs is size-dependent, and the smallest one (hydration diameter ca. 126 nm) is more efficient. Mechanistically, the high yields of photo-induced 1O2 by GFNPs can lead to the destruction of the tumor vascular endothelial adherent junction protein-VE cadherin and the decrease of tumor vascular endothelial cells-CD31 proteins, inducing the rapid tumor necrosis. In conclusion, our work provides an insight into the design of well-sized nanoparticles to powerfully treat the melanoma assisted by light, as well as greatly extends the applications of PDT for robust tumor therapy.