Ultrasound-Propelled Nanocups for Drug Delivery.
Ultrasound-Propelled Nanocups for Drug Delivery.
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DOI：
10.1002/smll.201501322
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发表时间：
2015-10-21
期刊：
影响因子：
--
通讯作者：
Coussios CC
中科院分区：
文献类型：
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作者：
Kwan JJ;Myers R;Coviello CM;Graham SM;Shah AR;Stride E;Carlisle RC;Coussios CC
超声诱导的气泡活动（空化）最近被证明可以积极运输和改善肿瘤中治疗剂的分布。然而，现有的空化促进剂是微米级的，不能在长时间内维持空化活性，因为它们在超声照射下会迅速被破坏。一种新型超声响应的单腔聚合物纳米颗粒（纳米杯）能够捕获和稳定气体，防止溶解在血液中。在现有诊断和治疗系统可达到的频率和强度的超声照射下，纳米杯启动并维持易于检测的空化活动，至少比在体内肿瘤模型中现有的微泡结构长四倍。当肿瘤暴露在超声波中时，静脉注射纳米杯也被发现可以改善自由循环的IgG小鼠抗体的分布，这是纳米杯增强未经修饰的治疗方法的能力的概念证明。在体外流动模型中，对纳米杯和共给药治疗模型的递送距离和浓度的定量分析表明，超声推动的纳米杯比治疗模型走得更远，而治疗模型本身被递送到离血管壁数百微米的地方。因此，纳米杯在增强肿瘤和其他生物医学应用中的药物输送和治疗监测方面具有相当大的潜力。
Ultrasound-induced bubble activity (cavitation) has been recently shown to actively transport and improve the distribution of therapeutic agents in tumors. However, existing cavitation-promoting agents are micron-sized and cannot sustain cavitation activity over prolonged time periods because they are rapidly destroyed upon ultrasound exposure. A novel ultrasound-responsive single-cavity polymeric nanoparticle (nanocup) capable of trapping and stabilizing gas against dissolution in the bloodstream is reported. Upon ultrasound exposure at frequencies and intensities achievable with existing diagnostic and therapeutic systems, nanocups initiate and sustain readily detectable cavitation activity for at least four times longer than existing microbubble constructs in an in vivo tumor model. As a proof-of-concept of their ability to enhance the delivery of unmodified therapeutics, intravenously injected nanocups are also found to improve the distribution of a freely circulating IgG mouse antibody when the tumor is exposed to ultrasound. Quantification of the delivery distance and concentration of both the nanocups and coadministered model therapeutic in an in vitro flow phantom shows that the ultrasound-propelled nanocups travel further than the model therapeutic, which is itself delivered to hundreds of microns from the vessel wall. Thus nanocups offer considerable potential for enhanced drug delivery and treatment monitoring in oncological and other biomedical applications.