Trimodal Therapy: Combining Hyperthermia with Repurposed Bexarotene and Ultrasound for Treating Liver Cancer.
Trimodal Therapy: Combining Hyperthermia with Repurposed Bexarotene and Ultrasound for Treating Liver Cancer.
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DOI：
10.1021/acsnano.5b05974
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发表时间：
2015-11-24
期刊：
影响因子：
17.1
通讯作者：
Pan D
中科院分区：
文献类型：
--
作者：
Misra SK;Ghoshal G;Gartia MR;Wu Z;De AK;Ye M;Bromfield CR;Williams EM;Singh K;Tangella KV;Rund L;Schulten K;Schook LB;Ray PS;Burdette EC;Pan D
改变现有抗癌药物的用途以克服其物理局限性，如不溶性，是实现更高疗效和扩大临床应用范围的一种有吸引力的策略。这种方法还有望在药物开发工作中节省大量成本。在这里，我们使用重新调整用途的FDA批准的局部药物贝沙罗汀(塔格列汀™)，目前仅限于T细胞淋巴瘤的皮肤表现，并通过形成自组装纳米气泡来重新设计它，以用于实体肿瘤应用。新型前药纳米泡泡的物理化学表征表明，在聚焦超声能量作用下，其稳定性、增强的靶细胞内化能力和高度可控的释放曲线。使用体外肝细胞癌模型和体内大动物肝脏消融模型，我们展示了贝沙罗汀前药纳米气泡与导管超声联合使用时的有效性，从而强调了这种三模式方法的治疗前景。
Repurposing of existing cancer drugs to overcome their physical limitations, such as insolubility, represents an attractive strategy to achieve enhanced therapeutic efficacy and broaden the range of clinical applications. Such an approach also promises to offer substantial cost savings in drug development efforts. Here we use repurposed FDA-approved topical agent bexarotene (Targretin™), currently in limited use for cutaneous manifestations of T-cell lymphomas, and re-engineer it for use in solid tumor applications by forming self-assembling nanobubbles. Physicochemical characterization studies of the novel prodrug nanobubbles demonstrated their stability, enhanced target cell-internalization capability and highly controlled release profile in response to application of focused ultrasound energy. Using an in vitro model of hepatocellular carcinoma and an in vivo large animal model of liver ablation, we demonstrate the effectiveness of bexarotene prodrug nanobubbles when used in conjunction with catheter-based ultrasound, thereby highlighting the therapeutic promise of this trimodal approach.