Ultrasound-Triggered Delivery of Anticancer Therapeutics from MRI-Visible Multilayer Microcapsules
Ultrasound-Triggered Delivery of Anticancer Therapeutics from MRI-Visible Multilayer Microcapsules
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DOI：
10.1002/adtp.201800051
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发表时间：
2018-09-01
影响因子：
4.6
通讯作者：
Kharlampieva, Eugenia
中科院分区：
文献类型：
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作者：
Alford, Aaron;Rich, Megan;Kharlampieva, Eugenia
尽管成像引导的药物递送代表了手术切除和全身方法的非侵入性替代方案，但由于目前可用的成像剂的潜在毒性和快速清除，其临床应用有限。在这里，我们介绍了治疗诊断生物相容性微胶囊作为有效的对比增强成像剂，结合联合收割机磁共振成像（MRI）与超声触发的药物释放的实时跟踪和靶向输送体内。3 μ m直径的胶囊是通过天然多酚单宁酸和聚（N-乙烯基吡咯烷酮）与4纳米氧化铁纳米粒子结合在胶囊壁中的逐层沉积组装的。纳米颗粒修饰的胶囊在临床3 T MRI扫描仪中表现出优异的T1和T2 MRI对比度。装载抗癌药物阿霉素，这些胶囊在血流中循环至少48小时，这是一个显着的改善相比，非封装纳米粒子。聚焦超声的应用导致靶向药物释放，与乳腺癌小鼠模型中的脱靶器官相比，肿瘤中的阿霉素定位增加了16倍。由于活性对比度，长循环，可定制的尺寸，形状，成分和高有效载荷浓度的精确递送，这些材料为成像引导的精确药物递送提供了强大而安全的平台。
Although imaging-guided drug delivery represents a noninvasive alternative to both surgical resection and systemic methods, it has seen limited clinical use due to the potential toxicity and fast clearance of currently available imaging agents. Herein, we introduce theranostic biocompatible microcapsules as efficient contrast-enhanced imaging agents that combine magnetic resonance imaging (MRI) with ultrasound-triggered drug release for real-time tracking and targeted delivery in vivo. The 3-mu m diameter capsules are assembled via layer-by-layer deposition of the natural polyphenol tannic acid and poly(N-vinylpyrrolidone) with 4 nm iron oxide nanoparticles incorporated in the capsule wall. The nanoparticle-modified capsules exhibit excellent T1 and T2 MRI contrast in a clinical 3T MRI scanner. Loaded with the anticancer drug doxorubicin, these capsules circulate in the blood stream for at least 48 h, which is a remarkable improvement compared to nonencapsulated nanoparticles. The application of focused ultrasound results in targeted drug release with a 16-fold increase in doxorubicin localization in tumors compared to off-target organs in a mouse model of breast cancer. Owing to the active contrast, long circulation, customizable size, shape, composition, and precise delivery of high payload concentrations, these materials present a powerful and safe platform for imaging-guided precision drug delivery.