2010年发表的两篇金属富勒烯抗肿瘤论文,均被美国国家健康研究院国家癌症研究所(NIH/NCI)选为肿瘤纳米技术新闻,并在其网站上加以报道。
链接网址:http://nano.cancer.gov/action/news/2010/may/nanotech_news_2010-05-21g.asp
这两篇论文简况:
1. PNAS April 20, 2010 vol. 107 no. 16 7449-7454
题目: Metallofullerene nanoparticles circumvent tumor resistance to cisplatin by reactivating endocytosis
作者: Xing-Jie Liang, Huan Meng , Yingze Wang, Haiyong He, Jie Meng , Juan Lu, Paul C. Wang, Yuliang Zhao , Xueyun Gao, Baoyun Sun, Chunying Chen, Genmei Xing, Dingwu Shen,Michael M. Gottesman, Yan Wu, Jun-jie Yin, and Lee Jia
Address correspondence to: liangxj@nanoctr.cn or zhaoyuliang@mail.ihep.ac.cn
摘要:Cisplatin is a chemotherapeutic drug commonly used in clinics. However, acquired resistance confines its application in chemotherapeutics. To overcome the acquired resistance to cisplatin, it is reasoned, based on our previous findings of mediation of cellular responses by [Gd@C82(OH)22]n nanoparticles, that [Gd@C82(OH)22]n may reverse tumor resistance to cisplatin by reactivating the impaired endocytosis of cisplatin-resistant human prostate cancer (CP-r) cells. Here we report that exposure of the CP-r PC-3-luc cells to cisplatin in the presence of nontoxic [Gd@C82(OH)22]n not only decreased the number of surviving CP-r cells but also inhibited growth of the CP-r tumors in athymic nude mice as measured by both optical and MRI. Labeling the CP-r PC-3 cells with transferrin, an endocytotic marker, demonstrated that pretreatment of the CP-r PC-3-luc cells with [Gd@C82(OH)22]n enhanced intracellular accumulation of cisplatin and formation of cisplatin-DNA adducts by restoring the defective endocytosis of the CP-r cancer cells. The results suggest that [Gd@C82(OH)22]n nanoparticles overcome tumor resistance to cisplatin by increasing its intracellular accumulation through the mechanism of restoring defective endocytosis. The technology can be extended to other challenges related to multidrug resistance often found in cancer treatments.
2. ACS Nano, 2010, 4 (5), pp 2773–2783
题目: Potent Angiogenesis Inhibition by the Particulate Form of Fullerene Derivatives
作者: Huan Meng, Gengmei Xing, Baoyun Sun, Feng Zhao, Hao Lei, Wei Li, Yan Song, Zhen Chen, Hui Yuan, Xuxia Wang, Jing Long, Chunying Chen, Xingjie Liang, Ning Zhang, Zhifang Chai and Yuliang Zhao
Address correspondence to zhaoyuliang@ihep.ac.cn
摘要:
Antiangiogenesis is an effective strategy for cancer treatment because uncontrolled tumor growth depends on tumor angiogenesis and sufficient blood supply. Great progress has been made in developing a “molecular” form of angiogenesis inhibitors; however, the narrow inhibition spectrum limits anticancer efficacy as those inhibitors that usually target a few or even a single angiogenic factor among many angiogenic factors might initially be effective but ultimately lead to the failure of the treatment due to the induction of expression of other angiogenic factors. In this work, we report that with a multiple hydroxyl groups functionalized surface, the Gd@C82(OH)22 fullerenic nanoparticles (f-NPs) are capable of simultaneously downregulating more than 10 angiogenic factors in the mRNA level that is further confirmed at the protein level. After studying this antiangiogenesis activity of the f-NPs by cellular experiment, we further investigated its anticancer efficacy in vivo. A two-week treatment with the f-NPs decreased >40% tumor microvessels density and efficiently lowered the speed of blood supply to tumor tissues by 40%. Efficacy of the treatment using f-NPs in nude mice was comparable to the clinic anticancer drug paclitaxel, while no pronounced side effects were found. These findings indicate that the f-NPs with multiple hydroxyl groups serve as a potent antiangiogenesis inhibitor that can simultaneously target multiple angiogenic factors. We propose that using nanoscale “particulate” itself as a new form of medicine (particulate medicine) may be superior to the traditional “molecular” form of medicine (molecular medicine) in cancer treatment.
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