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

Abstract

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.

• Authors: Mirong Guan, Yue Zhou, Shuai Liu, Daiqin Chen, Jiechao Ge, Ruijun Deng, Xue Li, Tong Yu, Hui Xu, Di Sun, Jiajia Zhao, Toujun Zou, Chunru Wang, Chunying Shu
• Journal: Biomaterials (Biomaterials) Vol. 213 Pg. 119218 (08 2019) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 31136911 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019. Published by Elsevier Ltd.

Chemical References

• Antineoplastic Agents
• Fullerenes
• Photosensitizing Agents
• Reactive Oxygen Species
• Tumor Necrosis Factor-alpha
• gadofullerene
• Interleukin-12
• MMP2 protein, human
• Matrix Metalloproteinase 2
• MMP9 protein, human
• Matrix Metalloproteinase 9

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology, therapeutic use)
• CD4-Positive T-Lymphocytes (cytology)
• CD8-Positive T-Lymphocytes (cytology)
• Cell Line, Tumor
• Dendritic Cells (metabolism)
• Female
• Fullerenes (chemistry, pharmacology, therapeutic use)
• Human Umbilical Vein Endothelial Cells
• Humans
• Immune System
• Interleukin-12 (metabolism)
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Mice
• Mice, Inbred BALB C
• Neoplasm Metastasis
• Neoplasms (blood supply, drug therapy)
• Neovascularization, Pathologic
• Photosensitizing Agents (chemistry, pharmacology, therapeutic use)
• Reactive Oxygen Species (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)