Laboratory of Controllable Preparation and Application of Nanomaterials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190, China.
ACS Nano. 2010 Nov 23;4(11):6874-82. doi: 10.1021/nn100918a. Epub 2010 Oct 25.
Mesoporous silica nanomaterial is one of the most promising candidates as drug carrier for cancer therapy. Herein, in vitro and in vivo study of silica nanorattle (SN) with mesoporous and rattle-type structure as a drug delivery system was first reported. Hydrophobic antitumor drug docetaxel (Dtxl) was loaded into the PEGylated silica nanorattle (SN-PEG) with a diameter of 125 nm via electrostatic absorption. In human liver cancer cell Hep-G2, the half-maximum inhibiting concentration (IC(50)) of silica nanorattle encapsulated docetaxel (SN-PEG-Dtxl) was only 7% of that of free Dtxl at 72 h. In vivo toxicity assessment showed that both nanocarrier of silica nanorattle (40 mg/kg, single dose) and SN-PEG-Dtxl (20 mg/kg of Dtxl, three doses) had low systematic toxicity in healthy ICR mice. The SN-PEG-Dtxl (20 mg/kg, intravenously) showed greater antitumor activity with about 15% enhanced tumor inhibition rate compared with Taxotere on the marine hepatocarcinoma 22 subcutaneous model. The results prove that the SN-PEG-Dtxl has low toxicity and high therapy efficacy, which provides convincing evidence for the silica nanorattle as a promising candidate for a drug delivery system.
介孔硅纳米材料是癌症治疗药物载体最有前途的候选材料之一。本文首次报道了具有介孔和笼型结构的硅纳米笼（SN）作为药物传递系统的体外和体内研究。疏水性抗肿瘤药物多西紫杉醇（Dtxl）通过静电吸附载入到直径为 125nm 的聚乙二醇化硅纳米笼（SN-PEG）中。在人肝癌细胞 Hep-G2 中，SN-PEG-Dtxl 的半最大抑制浓度（IC（50））在 72 小时时仅为游离 Dtxl 的 7%。体内毒性评估表明，在健康 ICR 小鼠中，硅纳米笼（40mg/kg，单次剂量）和 SN-PEG-Dtxl（20mg/kg 的 Dtxl，三剂）这两种纳米载体的系统毒性都很低。SN-PEG-Dtxl（20mg/kg，静脉内）在海洋肝癌 22 皮下模型上的抗肿瘤活性比 Taxotere 提高了约 15%，肿瘤抑制率提高了 15%。结果证明，SN-PEG-Dtxl 具有低毒性和高治疗效果，为硅纳米笼作为一种有前途的药物传递系统提供了令人信服的证据。
