超声空化增强介孔二氧化硅纳米粒的药物控释
Ultrasound-mediated Cavitation-enhanced extravasation of mesoporous silica nanoparticles for controlled-release drug delivery
摘要：
介孔二氧化硅纳米颗粒已被报道为合适的药物载体，但它们在全身给药后成功递送至靶组织仍然是一个挑战。在目前的工作中，超声诱导的惯性空化被评估为一种机制，以促进其外渗在流过组织模仿琼脂糖幻影。使用两种不同的超声频率（0.5或1.6MHz）和0.5-4 MPa范围内的压力来驱动实时检测的空化活性。确定的最佳超声条件被用来提供染料负载的纳米颗粒作为模型的药物负载的纳米载体，与外渗的水平通过荧光显微镜评价。然后将相同的纳米颗粒与亚微米聚合物空化核共注射，作为促进空化活性和降低获得外渗所需的原位声压的手段。将该组合的整体空化能和穿透力与单独的介孔二氧化硅纳米颗粒进行比较。本工作的结果表明，结合介孔二氧化硅纳米载体和亚微米空化核可能有助于增强纳米载体的外渗，从而使随后的持续药物释放发生从那些颗粒已经嵌入肿瘤组织。
英文摘要：
Mesoporous silica nanoparticles have been reported as suitable drug carriers, but their successful delivery to target tissues following systemic administration remains a challenge. In the present work, ultrasound-induced inertial cavitation was evaluated as a mechanism to promote their extravasation in a flow-through tissue-mimicking agarose phantom. Two different ultrasound frequencies, 0.5 or 1.6 MHz, with pressures in the range 0.5-4 MPa were used to drive cavitation activity which was detected in real time. The optimal ultrasound conditions identified were employed to deliver dye-loaded nanoparticles as a model for drug-loaded nanocarriers, with the level of extravasation evaluated by fluorescence microscopy. The same nanoparticles were then co-injected with submicrometric polymeric cavitation nuclei as a means to promote cavitation activity and decrease the required in-situ acoustic pressure required to attain extravasation. The overall cavitation energy and penetration of the combination was compared to mesoporous silica nanoparticles alone. The results of the present work suggest that combining mesoporous silica nanocarriers and submcrometric cavitation nuclei may help enhance the extravasation of the nanocarrier, thus enabling subsequent sustained drug release to happen from those particles already embedded in the tumour tissue.
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