Capacity of mesoporous bioactive glass nanoparticles to deliver therapeutic molecules
Capacity of mesoporous bioactive glass nanoparticles to deliver therapeutic molecules
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DOI：
10.1039/c2nr31775c
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发表时间：
2012-01-01
期刊：
影响因子：
6.7
通讯作者：
Kim, Hae-Won
中科院分区：
文献类型：
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作者：
El-Fiqi, Ahmed;Kim, Tae-Hyun;Kim, Hae-Won
无机生物活性纳米材料对于硬组织再生是有吸引力的，包括用于骨替代复合材料的纳米组分和用于递送治疗剂的纳米载体。生物活性玻璃纳米颗粒（BGn）最近获得了潜在的有用性，作为骨和牙齿再生剂。在这里，我们证明了具有介孔的BGn装载和递送治疗分子（药物，特别是基因）的能力。通过超声反应的溶胶-凝胶过程制备了尺寸为80-90 nm的球形BGn，以获得3-5 nm尺寸的介孔。介孔BGn的模拟体液测试证实了它们优异的磷灰石形成能力，并且细胞毒性研究证明了它们高达100 μ g/ml的良好细胞活力。考虑到纳米颗粒的中孔尺寸，引入小分子如化学药物（钠氨苄青霉素）和基因（小干扰RNA; siRNA）作为模型药物。此外，胺官能化允许BGn的可切换表面电荷性质（从-20-30 mV到+20-30 mV）。氨苄青霉素或siRNA的负载在几小时内饱和（类似于2小时）并反映了中孔结构。虽然氨苄青霉素释放相对较快（类似于12小时），但siRNA持续释放长达3天，几乎为零级动力学。SiRNA纳米颗粒很容易被细胞吸收，转染效率高达80%左右。如通过使用bcl-2模型基因检查的，从BGn递送的siRNA的沉默效果显示出显著的下调（与对照的15%相似），这表明BGn作为基因的新型纳米载体的潜在用途。这与其他有吸引力的性质，包括尺寸和介孔相关的高表面积和孔体积，可调的表面化学，磷灰石形成能力，良好的细胞活力和可能的离子相关的刺激作用，将加强BGn在硬组织再生中的有用性。
Inorganic bioactive nanomaterials are attractive for hard tissue regeneration, including nanocomponents for bone replacement composites and nanovehicles for delivering therapeutics. Bioactive glass nanoparticles (BGn) have recently gained potential usefulness as bone and tooth regeneratives. Here we demonstrate the capacity of the BGn with mesopores to load and deliver therapeutic molecules (drugs and particularly genes). Spherical BGn with sizes of 80-90 nm were produced to obtain 3-5 nm sized mesopores through a sono-reacted sol-gel process. A simulated body fluid test of the mesoporous BGn confirmed their excellent apatite forming ability and the cellular toxicity study demonstrated their good cell viability up to 100 mu g ml(-1). Small molecules like chemical drug (Na-ampicillin) and gene (small interfering RNA; siRNA) were introduced as model drugs considering the mesopore size of the nanoparticles. Moreover, amine-functionalization allowed switchable surface charge property of the BGn (from -20-30 mV to +20-30 mV). Loading of ampicillin or siRNA saturated within a few hours (similar to 2 h) and reflected the mesopore structure. While the ampicillin released relatively rapidly (similar to 12 h), the siRNA continued to release up to 3 days with almost zero-order kinetics. The siRNA-nanoparticles were easily taken up by the cells, with a transfection efficiency as high as similar to 80%. The silencing effect of siRNA delivered from the BGn, as examined by using bcl-2 model gene, showed dramatic down-regulation (similar to 15% of control), suggesting the potential use of BGn as a new class of nanovehicles for genes. This, in conjunction with other attractive properties, including size-and mesopore-related high surface area and pore volume, tunable surface chemistry, apatite-forming ability, good cell viability and the possible ion-related stimulatory effects, will potentiate the usefulness of the BGn in hard tissue regeneration.