Laboratory of Controllable Preparation and Application of Nanomaterials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
Biomaterials. 2010 Aug;31(24):6142-53. doi: 10.1016/j.biomaterials.2010.04.055. Epub 2010 May 26.
The concept that mesoporous silica nanoparticles (MSNs) are regarded as ideal novel drug delivery carriers in tumor therapy has been introduced extensively, but the effects of MSNs on tumor growth have received little attention. Here a model of nude mice xenografted with human malignant melanoma cells (A375) was used to investigate the effect of MSNs on tumor growth. Surprisingly, we found that MSNs have no toxicity to human malignant melanoma but increasing tumor growth in vivo. It was also confirmed that MSNs significantly promoted A375 cell proliferation and accelerated cell cycle progression in vitro. Cellular uptake mechanism showed that MSNs may affect molecular behavior of A375 cells when they entered into cytoplasm. Then, a detailed mechanism indicated that the promotion effect induced by MSNs was due to the decreasing of endogenous reactive oxygen species (ROS) in cells. Further results demonstrated that the upregulation of anti-apoptotic molecules Bcl-2 expression and the inhibition of NF-kappaB activation by MSNs may promote cell proliferation in a redox-sensitive signal pathway. These results show that tumor growth can be regulated by nanocarriers themselves in a ROS-dependent manner and imply that nanocarriers are not necessarily suitable for all kinds of tumor therapy in development drug delivery system.
介孔硅纳米粒子（MSNs）被广泛认为是肿瘤治疗中理想的新型药物载体，但 MSNs 对肿瘤生长的影响却很少受到关注。在这里，我们使用裸鼠人恶性黑色素瘤细胞（A375）异种移植模型来研究 MSNs 对肿瘤生长的影响。令人惊讶的是，我们发现 MSNs 对人恶性黑色素瘤没有毒性，但能在体内促进肿瘤生长。体外实验也证实 MSNs 能显著促进 A375 细胞增殖，并加速细胞周期进程。细胞摄取机制表明，MSNs 进入细胞质时可能会影响 A375 细胞的分子行为。然后，详细的机制表明，MSNs 诱导的促进作用是由于细胞内内源性活性氧（ROS）的减少。进一步的结果表明，MSNs 上调抗凋亡分子 Bcl-2 的表达并抑制 NF-kappaB 的激活，可能通过氧化还原敏感信号通路促进细胞增殖。这些结果表明，肿瘤生长可以通过纳米载体本身以 ROS 依赖的方式进行调节，并暗示纳米载体在开发药物输送系统时不一定适用于所有类型的肿瘤治疗。
