Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway.
J Control Release. 2014 Aug 10;187:39-49. doi: 10.1016/j.jconrel.2014.05.020. Epub 2014 May 20.
The delivery of nanoparticles to solid tumors is often ineffective due to the lack of specificity towards tumor tissue, limited transportation of the nanoparticles across the vascular wall and poor penetration through the extracellular matrix of the tumor. Ultrasound is a promising tool that can potentially improve several of the transportation steps, and the interaction between sound waves and microbubbles generates biological effects that can be beneficial for the successful delivery of nanocarriers and their contents. In this study, a novel platform consisting of nanoparticle-stabilized microbubbles has been investigated for its potential for ultrasound-enhanced delivery to tumor xenografts. Confocal laser scanning microscopy was used to study the supply of nanoparticles from the vasculature and to evaluate the effect of different ultrasound parameters at a microscopic level. The results demonstrated that although the delivery is heterogeneous within tumors, there is a significant improvement in the delivery and the microscopic distribution of both nanoparticles and a released model drug when the nanoparticles are combined with microbubbles and ultrasound. The mechanisms that underlie the improved delivery are discussed.
由于缺乏对肿瘤组织的特异性、纳米颗粒在血管壁中的有限传输以及穿过肿瘤细胞外基质的能力差,纳米颗粒向实体瘤的输送通常效果不佳。超声是一种很有前途的工具,它有可能改善几种输送步骤,而且声波与微泡的相互作用会产生有益于成功输送纳米载体及其内容物的生物学效应。在这项研究中,研究了由纳米颗粒稳定的微泡组成的新型平台,以研究其对肿瘤异种移植物的超声增强输送的潜力。共聚焦激光扫描显微镜用于从血管供应中研究纳米颗粒,并在微观水平上评估不同超声参数的效果。结果表明,尽管肿瘤内的输送存在异质性,但当纳米颗粒与微泡和超声结合使用时,纳米颗粒和释放的模型药物的输送和微观分布都有显著改善。讨论了改善输送的潜在机制。
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