A highly efficient and tumor vascular-targeting therapeutic technique with size-expansible gadofullerene nanocrystals

Abstract

It has long been a dream to achieve tumor targeting therapy that can efficiently reduce the toxicity and severe side effects of conventional antitumor chemotherapeutic agents. Taking advantage of the abnormalities of tumor vasculature, we demonstrate here a new powerful tumor vascular-targeting therapeutic technique for solid cancers that applies advanced nanotechnology to cut off the nutrient supply of tumor cells by physically destroying the abnormal tumor blood vessels. Water soluble magnetic Gd@C82 nanocrystals of the chosen sizes are deliberately designed with abilities to penetrate into the leaky tumor blood vessels. By triggering the radiofrequency induced phase transition of gadofullerene nanocrystals while extravasating the tumor blood vessel, the explosive structural change of nanoparticles generates a devastating impact on abnormal tumor blood vessels, resulting in a rapid and extensive ischemia necrosis and shrinkage of the tumors. This unprecedented target-specific physiotherapy is found to work perfectly for advanced and refractory solid tumors.

中文摘要

本文报道了一种利用金属富勒烯纳米晶体快速高效治疗肿瘤的新技术. 从生物学上肿瘤血管和正常血管在结构上存在显著差异这一特点着手, 利用材料学上金属富勒烯纳米晶体在吸收射频能量后发生相变, 伴随着体积剧烈膨胀的特性, 高选择性地摧毁肿瘤血管. 研究表明, 经过1小时治疗后, 肿瘤部位血流即可发生快速阻断, 治疗2~4小时后, 肿瘤组织逐步发生出血性坏死, 肿瘤塌陷体积缩小; 并且对于多种实体肿瘤均有显著疗效. 该技术是一种快速、广谱、特异性高、毒副作用小的新型肿瘤治疗技术, 是一种具有巨大发展潜力的肿瘤治疗技术.

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Corresponding author

Correspondence to Chunru Wang.

Additional information

Acknowledgments This work was supported by the National Natural Science Foundation of China (51472248, 11179006 and 51372251) and the Key Research Program of the Chinese Academy of Sciences (KGZDEW- T02 and XDA09030302). We thank Prof. Yan Li of Zhongnan Hospital of Wuhan University for help with tissues histology and biochemical analysis. We also thank Yongtao Li, Zhentao Zuo, and Yuqing Wang for developing the RF set-ups.

Author contributions Wang C and Zhen M supervised the project and designed the experiments. Li J synthesized the GFNCs. Zhen M and Zhang G performed the in vivo experiments. Zhen M, Deng R and Zou T performed the in vitro characterization. Shu C and Wang T analyzed the nature of GFNCs. Fang F and Lei H performed the animal MRI studies. Wang C, Bai C and Luo Y contributed to the interpretation of the data. Zhen M, Luo Y and Wang C wrote the manuscript.

Conflict of interests The authors declare that they have no conflict of interest.

Supplementary information Supporting data are available in the online version of the paper.

Mingming Zhen was born in 1987. She received her PhD degree in physical chemistry from the Institute of Chemistry, Chinese Academy of Sciences (ICCAS) in 2014. Currently, she is an assistant professor at ICCAS. Her research interests include biomedical applications of fullerenes and gadofullerenes

Chunru Wang was born in 1965. He received his PhD degree in physical chemistry from Dalian Institute of Chemistry Physics, Chinese Academy of Sciences in 1992. Currently, he is a professor at ICCAS. His research interests include fullerenes and endohedral fullerenes, mainly focusing on their industrialization and applications. He discovered the metal carbide fullerenes for the first time, researched on high efficiency MRI contrast agents and developed a novel tumor vascular-targeting therapy technique using gadofullerenes.

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Zhen, M., Shu, C., Li, J. et al. A highly efficient and tumor vascular-targeting therapeutic technique with size-expansible gadofullerene nanocrystals. Sci. China Mater. 58, 799–810 (2015). https://doi.org/10.1007/s40843-015-0089-3

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Keywords

  • Fullerene
  • Environmental Scanning Electron Microscopy
  • Tumor Blood Vessel
  • Science China Material
  • Magnetic Resonance Angiography Image