High intensity focused ultrasound hyperthermia for enhanced macromolecular delivery
High intensity focused ultrasound hyperthermia for enhanced macromolecular delivery
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DOI：
10.1016/j.jconrel.2016.09.030
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发表时间：
2016-11-10
影响因子：
10.8
通讯作者：
Ghandehari, Hamidreza
中科院分区：
文献类型：
--
作者：
Frazier, Nick;Payne, Allison;Ghandehari, Hamidreza
轻度热疗已与聚合物治疗剂组合使用，以进一步增加对实体瘤的递送并提高疗效。用于产生热量的有吸引力的方法是通过非侵入性高强度聚焦超声（HIFU）。HIFU通常用于消融治疗，并且必须适于在实体瘤中产生均匀的轻度高温。在这项工作中，磁共振成像引导的高强度聚焦超声（MRgHIFU）控制的反馈系统的开发，以产生一个空间均匀的43摄氏度的加热模式在皮下小鼠肿瘤。采用MRgHIFU来创建增强大分子递送的高热条件。使用具有两个皮下肿瘤的小鼠模型，证明了MRgHIFU增强埃文斯蓝染料（EBD）和钆螯合的N-（2-羟丙基）甲基丙烯酰胺（HPMA）共聚物的递送。与未加热的肿瘤相比，加热的肿瘤中的EBD积累增加了近2倍。钆螯合HPMA共聚物也显示出显着增强的积累超过控制通过MRI T1-映射测量评价。结果显示HIFU介导的热疗用于增强聚合物治疗剂的递送的潜力。(C)© 2016 Elsevier B. V.版权所有。
Mild hyperthermia has been used in combination with polymer therapeutics to further increase delivery to solid tumors and enhance efficacy. An attractive method for generating heat is through non-invasive high intensity focused ultrasound (HIFU). HIFU is often used for ablative therapies and must be adapted to produce uniform mild hyperthermia in a solid tumor. In this work a magnetic resonance imaging guided HIFU (MRgHIFU) controlled feedback system was developed to produce a spatially uniform 43 degrees C heating pattern in a subcutaneous mouse tumor. MRgHIFU was employed to create hyperthermic conditions that enhance macromolecular delivery. Using a mouse model with two subcutaneous tumors, it was demonstrated that MRgHIFU enhanced delivery of both Evans blue dye (EBD) and Gadolinium-chelated N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers. The EBD accumulation in the heated tumors increased by nearly 2-fold compared to unheated tumors. The Gadolinium-chelated HPMA copolymers also showed significant enhancement in accumulation over control as evaluated through MRI T1-mapping measurements. Results show the potential of HIFU-mediated hyperthermia for enhanced delivery of polymer therapeutics. (C) 2016 Elsevier B.V. All rights reserved.