Potent Angiogenesis Inhibition by the Particulate Form of Fullerene Derivatives
Potent Angiogenesis Inhibition by the Particulate Form of Fullerene Derivatives
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DOI：
10.1021/nn100448z
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发表时间：
2010-05-01
期刊：
影响因子：
17.1
通讯作者：
Zhao, Yuliang
中科院分区：
文献类型：
--
作者：
Meng, Huan;Xing, Gengmei;Zhao, Yuliang
抗血管生成是治疗肿瘤的有效策略，因为不受控制的肿瘤生长依赖于肿瘤血管生成和足够的血液供应。在开发“分子”形式的血管生成抑制剂方面已经取得了很大进展;然而，狭窄的抑制谱限制了抗癌功效，因为通常靶向许多血管生成因子中的少数甚至单个血管生成因子的那些抑制剂可能最初有效，但最终由于诱导其他血管生成因子的表达而导致治疗失败。在这项工作中，我们报告了具有多个羟基功能化表面的Gd@C（82）（OH）（22）富勒烯纳米颗粒（f-NPs）能够在mRNA水平上同时下调10种以上的血管生成因子，这在蛋白质水平上得到了进一步证实。在通过细胞实验研究了f-NPs的这种抗血管生成活性之后，我们进一步研究了其体内抗癌功效。用f-NP治疗两周使肿瘤微血管密度降低>40%，并有效地将肿瘤组织的血液供应速度降低了约40%。在裸鼠体内，f-NPs的治疗效果与临床抗癌药物紫杉醇相当，而没有发现明显的副作用。这些发现表明，具有多个羟基的f-NPs作为一种有效的抗血管生成抑制剂，可以同时靶向多种血管生成因子。我们提出，利用纳米级“微粒”本身作为一种新的药物形式（微粒药物），在癌症治疗中可能上级传统的“分子”药物形式（分子药物）。
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@C(82)(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 similar to 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.