Real-time Monitoring of Tumor Vascular Disruption Induced by Radiofrequency Assisted Gadofullerene

The anti-vascular therapy has been extensively studied for high performance tumor therapy by suppressing the tumor angiogenesis or cutting off the existing tumor vasculature. We have previously reported a novel anti-tumor treatment technique using radiofrequency (RF)-assisted gadofullerene nanocrystals (GFNCs) to selectively disrupt the tumor vasculature. In this work, we further revealed the changes on morphology and functionality of the tumor vasculature during the high-performance RF-assisted GFNCs treatment in vivo. Here, a clearly evident mechanism of this technique in tumor vascular disruption was elucidated. Based on the H22 tumor bearing mice with dorsal skin flap chamber (DSFC) model and the dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) technique, it was revealed that the GFNCs would selectively inset in the gaps of tumor vasculature due to the innately incomplete structures and unique microenvironment of tumor vasculature, and they damaged the surrounding endothelia cells excited by the RF to induce a phase transition accompanying with size expansion. Soon afterwards, the blood flow of the tumor blood vessels was permanently shut off, causing the entire tumor vascular network to collapse within 24 h after the treatment. The RF-assistant GFNCs technique was proved to aim at the tumor vasculature precisely, and was harmless to the normal vasculature. The current studies provide a rational explanation on the high efficiency anticancer activity of the RF-assisted GFNCs treatment, suggesting a novel technique with potent clinical application.