Photo-triggered gadofullerene: enhanced cancer therapy by combining tumor vascular disruption and stimulation of anti-tumor immune responses

Efficient treatment of primary tumor and preventing cancer metastasis present intriguing alternatives to cancer therapy. Herein, for the first time, we reported the photo-triggered nano-gadofullerene (Gd@C82-Ala, abbreviated Gd-Ala) induced malignant tumor vascular disruption by shortening the light interval between Gd-Ala administration and light illumination, where oxygen in blood vessels was employed efficiently to produce cytotoxic reactive oxygen species (ROS). The produced ROS could not only destroy the tumor cells but also devastate the vascular endothelial cells corresponding to the loss of intercellular junctions and vessels disruption. Notably, the irradiated Gd-Ala could enhance dendritic cells (DCs) maturation, which further secreted tumor necrosis factor-α (TNF-α) and interleukin-12 (IL)-12, and then activated T lymphocytes by up-regulation of cluster of differentiation CD4+ and CD8+ T lymphocytes. Furthermore, the down-regulation of matrix metalloprotein 2 (MMP2) and MMP9 also reduce the rate of tumor metastasis. This work explored a new biomedical application of gadofullerene, thereby providing a smart carbon nanomaterial candidate for tumor ablation and inhibition of cancer metastasis.