Laboratory of Controllable Preparation and Application of Nanomaterials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190, China.
ACS Nano. 2011 Jul 26;5(7):5390-9. doi: 10.1021/nn200365a. Epub 2011 Jun 8.
In our previous study we reported that the interaction of nanoparticles with cells can be influenced by particle shape, but until now the effect of particle shape on in vivo behavior remained poorly understood. In the present study, we control the fabrication of fluorescent mesoporous silica nanoparticles (MSNs) by varying the concentration of reaction reagents especially to design a series of shapes. Two different shaped fluorescent MSNs (aspect ratios, 1.5, 5) were specially designed, and the effects of particle shape on biodistribution, clearance and biocompatibility in vivo were investigated. Organ distributions show that intravenously administrated MSNs are mainly present in the liver, spleen and lung (>80%) and there is obvious particle shape effects on in vivo behaviors. Short-rod MSNs are easily trapped in the liver, while long-rod MSNs distribute in the spleen. MSNs with both aspect ratios have a higher content in the lung after PEG modification. We also found MSNs are mainly excreted by urine and feces, and the clearance rate of MSNs is primarily dependent on the particle shape, where short-rod MSNs have a more rapid clearance rate than long-rod MSNs in both excretion routes. Hematology, serum biochemistry, and histopathology results indicate that MSNs would not cause significant toxicity in vivo, but there is potential induction of biliary excretion and glomerular filtration dysfunction. These findings may provide useful information for the design of nanoscale delivery systems and the environmental fate of nanoparticles.
在我们之前的研究中，我们报道了纳米颗粒与细胞的相互作用可以受到颗粒形状的影响，但直到现在，颗粒形状对体内行为的影响仍知之甚少。在本研究中，我们通过改变反应试剂的浓度来控制荧光介孔硅纳米颗粒（MSNs）的制备，特别是设计了一系列形状。我们特别设计了两种不同形状的荧光 MSNs（纵横比分别为 1.5 和 5），并研究了颗粒形状对体内分布、清除和生物相容性的影响。器官分布表明，静脉注射的 MSNs 主要存在于肝脏、脾脏和肺部（>80%），并且对体内行为有明显的颗粒形状影响。短棒状 MSNs 容易在肝脏中被捕获，而长棒状 MSNs 则分布在脾脏中。经 PEG 修饰后，两种形状的 MSNs 在肺部的含量都更高。我们还发现 MSNs 主要通过尿液和粪便排出，MSNs 的清除率主要取决于颗粒形状，其中短棒状 MSNs 在两种排泄途径中的清除率均高于长棒状 MSNs。血液学、血清生化和组织病理学结果表明，MSNs 在体内不会引起明显的毒性，但可能会诱导胆汁排泄和肾小球滤过功能障碍。这些发现可能为纳米级递药系统的设计和纳米颗粒的环境归宿提供有用的信息。
