CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.
ACS Nano. 2010 May 25;4(5):2773-83. doi: 10.1021/nn100448z.
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 approximately 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.
抗血管生成是癌症治疗的有效策略，因为不受控制的肿瘤生长依赖于肿瘤血管生成和充足的血液供应。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，抑制谱狭窄限制了抗癌疗效，因为那些通常针对多种血管生成因子中的少数甚至单个血管生成因子的抑制剂最初可能有效，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，我们报告说，具有多个羟基功能化表面的 Gd@C(82)(OH)(22)富勒烯纳米粒子（f-NPs）能够同时下调超过 10 种血管生成因子在 mRNA 水平，这在蛋白质水平进一步得到证实。在通过细胞实验研究了 f-NPs 的这种抗血管生成活性后，我们进一步在体内研究了其抗癌疗效。两周的 f-NPs 治疗使肿瘤微血管密度降低了>40%，并使肿瘤组织的血液供应速度降低了约 40%。f-NPs 在裸鼠中的治疗效果可与临床抗癌药物紫杉醇相媲美，而未发现明显的副作用。这些发现表明，具有多个羟基的 f-NPs 可作为一种有效的抗血管生成抑制剂，可同时针对多种血管生成因子。我们提出，使用纳米级“颗粒”本身作为一种新形式的药物（颗粒药物）可能优于传统的“分子”形式的药物（分子药物）在癌症治疗中的应用。
