The tumor vasculature with unique characteristics offers an attractive target for anti-cancer therapy. Herein we put forward a novel antitumor therapeutic mechanism based on the gadofullerene nanocrystals (GFNCs), the agent we have previously shown to efficiently disrupt tumor vasculature by size-expansion with assistance of radiofrequency (RF). However, the tumor vascular disrupting mechanism of RF-assisted GFNCs treatment was not further studied. In the present work, a rapid tumor blood flow shutdown has been observed by the vascular perfusion imaging in vivo and vascular damages were evident 6 h after the RF-assisted GFNCs treatment. Importantly, a significant down-expression of tumor vascular endothelial cadherin (VE-cadherin) treated by RF-assisted GFNCs was further investigated, which caused vascular collapse, blood flow shut-down and subsequent tumor hemorrhagic necrosis. These findings set forth a systematic mechanism on the superior anti-tumor efficiency by RF-assisted GFNCs treatment.

具有独特特征的肿瘤脉管系统为抗癌治疗提供了有吸引力的靶标。本文中，我们提出了一种基于the富勒烯纳米晶体（GFNCs）的新型抗肿瘤治疗机制，该药物先前已被证明可以借助射频（RF）的扩展来有效破坏肿瘤血管。然而，RF辅助的GFNCs治疗的肿瘤血管破坏机制没有进一步研究。在目前的工作中，已经通过体内的血管灌注成像观察到了肿瘤血流的快速关闭。射频辅助GFNCs治疗后6小时，血管损伤明显。重要的是，进一步研究了RF辅助GFNC处理后肿瘤血管内皮钙粘蛋白（VE-cadherin）的显着下调，其引起血管萎缩，血流关闭和随后的肿瘤出血坏死。这些发现为RF辅助的GFNC治疗提供了优异的抗肿瘤效率的系统机制。