Stepwise drug release from a nanoplatform under MR-assisted focused ultrasound stimulation
Stepwise drug release from a nanoplatform under MR-assisted focused ultrasound stimulation
复制标题
在 MR 辅助聚焦超声刺激下从纳米平台逐步释放药物
DOI：
10.1016/j.cej.2020.128004
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发表时间：
2021-05-12
影响因子：
15.1
通讯作者：
Chen, Hangrong
中科院分区：
文献类型：
--
作者：
Liu, Tianzhi;Wan, Qian;Chen, Hangrong
聚焦超声（FUS）控制的药物输送正在走向成熟，通过集成超声响应纳米载体和最先进的磁共振（MR）技术的高度精确和智能的方法。在此，超声响应纳米平台（Dox@L@FeHD）开发基于中空树枝状介孔有机硅纳米粒子（HDMONs）。使用简单的芬顿反应，超小的α-FeOOH物质被锚定在HDMON内，随后植入阿霉素（Dox）和L-薄荷醇（LM）以获得Dox@L@FeHD，其显示T-1-T-2双峰MR对比特征。在轻度高温条件（45 ℃）下，包封的LM在HDMONs内经历相变和重新分布（“流动”），导致刺激后Dox@L@FeHD的重排孔结构。因此，Dox从突释转变为持续释放，如通过MR成像由于同时改变Dox@L@FeHD的MR对比度特征而可视化的。Dox@L@FeHD的体内FUS刺激使用自主开发的反馈温度控制算法来执行，以在靶向肿瘤区域提供45 ° C的恒定温度，从而触发原位逐步释放Dox，其诱导肿瘤生长的有效阻滞。这项工作展示了智能介孔纳米载体和MR-FUS技术的精确调节药物释放动力学的精心婚姻。
Focused ultrasound (FUS) controlled drug delivery is maturing towards a highly precise and intelligent approach via the integration of ultrasound-responsive nanocarriers and the state-of-the-art magnetic resonance (MR) technique. Herein, an ultrasound-responsive nanoplatform (Dox@L@FeHD) is developed based on hollow dendritic mesoporous organosilica nanoparticles (HDMONs). Using a facile Fenton reaction, ultrasmall alpha-FeOOH species are anchored within HDMONs, followed by implanting both doxorubicin (Dox) and L-menthol (LM) to obtain Dox@L@FeHD, which shows a T-1-T-2 bimodal MR contrast feature. Under mild hyperthermia condition (45 degrees C), the encapsulated LM undergoes a phase-transition and redistribution ("flowing") within HDMONs, resulting in a rearranged pore structure of Dox@L@FeHD post stimulation. Consequently, Dox shifts from burst release to sustained release, as visualized by MR imaging due to the altered MR contrast feature of Dox@L@FeHD concurrently. In vivo FUS stimulation of Dox@L@FeHD is executed using a self-developed feedback temperature control algorithm to render a constant temperature of 45 degrees C at the targeted tumor region, thus triggering the in-situ stepwise Dox release, which induces effective retardation of tumor growth. This work demonstrates an elaborate marriage of smart mesoporous nanocarriers and the MR-FUS technique for the accurate regulation of drug release kinetics.