Beijing National Laboratory for Molecular Sciences, Key Laboratory of Molecular Nanostructure and Nanotechnology, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
Beijing National Laboratory for Molecular Sciences, Key Laboratory of Molecular Nanostructure and Nanotechnology, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
Biomaterials. 2018 May;163:142-153. doi: 10.1016/j.biomaterials.2018.02.028. Epub 2018 Feb 13.
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.
肿瘤血管具有独特的特征，为抗癌治疗提供了一个有吸引力的靶点。在此，我们提出了一种基于超分子纳米载体（GFNCs）的抗肿瘤治疗新机制，我们之前的研究表明，该纳米载体在射频（RF）的辅助下通过尺寸扩张能有效地破坏肿瘤血管。然而，RF 辅助 GFNCs 治疗的肿瘤血管破坏机制尚未进一步研究。在本工作中，通过体内血管灌注成像观察到快速的肿瘤血流关闭，并且在 RF 辅助 GFNCs 治疗后 6 小时观察到明显的血管损伤。重要的是，进一步研究了 RF 辅助 GFNCs 处理后肿瘤血管内皮钙黏蛋白（VE-cadherin）的显著下调，这导致了血管塌陷、血流关闭和随后的肿瘤出血性坏死。这些发现阐述了 RF 辅助 GFNCs 治疗具有优异抗肿瘤效率的系统机制。
