Department of Bioengineering, University of Utah, Salt Lake City, 84112, USA; Center for Nanomedicine, Nano Institute of Utah, University of Utah, Salt Lake City, 84112, USA.
Department of Radiology, University of Utah, Salt Lake City, 84112, USA.
J Control Release. 2016 Nov 10;241:186-193. doi: 10.1016/j.jconrel.2016.09.030. Epub 2016 Sep 27.
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°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.
轻度热疗已与聚合物治疗联合使用，以进一步增加对实体瘤的递药并提高疗效。一种有吸引力的产生热量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，必须进行调整以在实体瘤中产生均匀的轻度热疗。在这项工作中，开发了一种磁共振成像引导的 HIFU（MRgHIFU）控制反馈系统，以在皮下小鼠肿瘤中产生空间均匀的 43°C 加热模式。MRgHIFU 用于产生增强大分子递药的热疗条件。使用具有两个皮下肿瘤的小鼠模型，证明 MRgHIFU 增强了 Evans 蓝染料（EBD）和钆螯合 N-（2-羟丙基）甲基丙烯酰胺（HPMA）共聚物的递药。与未加热的肿瘤相比，加热肿瘤中的 EBD 积累增加了近 2 倍。通过 MRI T1 映射测量评估，钆螯合 HPMA 共聚物的积累也显示出明显的增强。结果表明，HIFU 介导的热疗有可能增强聚合物治疗的递药。
