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. 2017 Jul;133:107-118. doi: 10.1016/j.biomaterials.2017.04.025. Epub 2017 Apr 14.
Researchers have been puzzled of the therapy of malignant tumors and the current therapeutic strategies are always accompanied by toxicity or side effects. Developing efficient nanodrugs could reduce the dosage and greatly improve the therapeutic effects in cancer treatments. Here we initially reported a novel kind of gadofullerene nanoparticles functionalized with amino acid (β-alanine), which exhibited a superior antitumor activity in hepatoma H22 models via a novel therapeutic mechanism. The involvement of β-alanine improved the tumor inhibition rate up to 76.85% for a single treatment by strengthening the interaction with radiofrequency (RF) and extending blood circulation time. It realized a highly antivascular treatment to cut off the nutrient supply of tumor cells by physically destroying the abnormal tumor blood vessels assisted by RF. In situ and real-time observation of the vascular change was conducted using the dorsal skin fold chamber model, which corresponded to the erythrocyte diapedesis in histopathological examination. The ultrastructural changes of vascular endothelial cells were further investigated by environmental scanning electron microscopy and transmission electron microscopy. Long-term toxicity evaluation showed that the GF-Ala nanoparticles could be eliminated from the mice after several days and no obvious toxicity was found to the main organs. All these encouraging results suggest GF-Ala nanoparticles are valuable for the significant therapeutic potential with high-efficacy and low-toxicity.
研究人员一直对恶性肿瘤的治疗感到困惑，目前的治疗策略总是伴随着毒性或副作用。开发有效的纳米药物可以减少剂量，并在癌症治疗中大大提高治疗效果。在这里，我们首次报道了一种新型的氨基酸（β-丙氨酸）功能化的富勒烯纳米颗粒，它通过一种新的治疗机制在肝癌 H22 模型中显示出优异的抗肿瘤活性。β-丙氨酸的参与通过增强与射频（RF）的相互作用并延长血液循环时间，将单一治疗的肿瘤抑制率提高到 76.85%。它通过物理破坏射频辅助的异常肿瘤血管来实现高度抗血管治疗，从而切断肿瘤细胞的营养供应。使用背部皮肤折叠室模型进行了血管变化的原位和实时观察，这与组织病理学检查中的红细胞渗出相对应。通过环境扫描电子显微镜和透射电子显微镜进一步研究了血管内皮细胞的超微结构变化。长期毒性评估表明，GF-Ala 纳米颗粒在几天内可以从小鼠体内消除，并且对主要器官没有明显的毒性。所有这些令人鼓舞的结果表明，GF-Ala 纳米颗粒具有高效低毒的显著治疗潜力，非常有价值。
