A Responsive Mesoporous Silica Nanoparticle Platform for Magnetic Resonance Imaging-Guided High-Intensity Focused Ultrasound-Stimulated Cargo Delivery with Controllable Location, Time, and Dose
A Responsive Mesoporous Silica Nanoparticle Platform for Magnetic Resonance Imaging-Guided High-Intensity Focused Ultrasound-Stimulated Cargo Delivery with Controllable Location, Time, and Dose
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DOI：
10.1021/jacs.9b07591
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发表时间：
2019-11-06
影响因子：
15
通讯作者：
Zink, Jeffrey I.
中科院分区：
文献类型：
--
作者：
Cheng, Chi-An;Chen, Wei;Zink, Jeffrey I.
磁共振成像（MRI）是临床诊断的重要手段，MRI引导的高强度聚焦超声（MRgHIFU）是一种强大的靶向治疗技术。MRgHIFU的临床应用主要利用热疗和消融来治疗癌组织，但是对于药物递送应用，热损伤是不期望的。已经开发了一种生物友好的MRgHIFU响应性介孔二氧化硅纳米颗粒（MSN）平台，其在生理安全温度范围内受到刺激，从而降低了对周围健康组织的热损伤的可能性。采用生物相容性聚乙二醇（PEG）来覆盖MSN的孔，并且通过HIFU释放货物分子而没有显著的温度升高（类似于4摄氏度）。为了通过MRI可视化并测量原位刺激输送，使用美国食品和药物管理局（FDA）批准的钆基造影剂钆喷酸葡胺（Gd（DTPA）（2-））作为可成像货物。利用MRgHIFU的三维成像和靶向能力，在仿组织凝胶体模中，在三维空间中的HIFU焦点处精确定位由HIFU刺激的Gd（DTPA）（2-）的释放。Gd（DTPA）（2-）的释放量由HIFU刺激时间和功率水平控制。发现Gd（DTPA）（2-）释放量与T-1呈正相关。通过这项技术，可以跟踪纳米载体的生物分布，并可以精确定位MRgHIFU刺激的货物释放，为未来的图像引导治疗诊断应用开辟了机会。
Magnetic resonance imaging (MRI) is an essential modality for clinical diagnosis, and MRI-guided high-intensity focused ultrasound (MRgHIFU) is a powerful technology for targeted therapy. Clinical applications of MRgHIFU primarily utilize hyperthermia and ablation to treat cancerous tissue, but for drug delivery applications thermal damage is undesirable. A biofriendly MRgHIFU-responsive mesoporous silica nanoparticle (MSN) platform that is stimulated within a physiological safe temperature range has been developed, reducing the possibility of thermal damage to the surrounding healthy tissues. Biocompatible polyethylene glycol (PEG) was employed to cap the pores of MSNs, and the release of cargo molecules by HIFU occurs without substantial temperature increase (similar to 4 degrees C). To visualize by MRI and measure the stimulated delivery in situ, a U.S. Food and Drug Administration (FDA)-approvedgadolinium-based contrast agent, gadopentetate dimeglumine (Gd(DTPA)(2-)), was used as the imageable cargo. Taking advantage of the three-dimensional (3-D) imaging and targeting capabilities of MRgHIFU, the release of Gd(DTPA)(2-) stimulated by HIFU was pinpointed at the HIFU focal point in 3-D space in a tissue-mimicking gel phantom. The amount of Gd(DTPA)(2-) released was controlled by HIFU stimulation times and power levels. A positive correlation between the amount of Gd(DTPA)(2-) released and T-1 was found. The MRgHIFU-stimulated cargo release was further imaged in a sample of ex vivo animal tissue. With this technology, the biodistribution of the nanocarriers can be tracked and the MRgHIFU-stimulated cargo release can be pinpointed, opening up an opportunity for future image-guided theranostic applications.