A FRET-guided, NIR-responsive bubble-generating liposomal system for in vivo targeted therapy with spatially and temporally precise controlled release
A FRET-guided, NIR-responsive bubble-generating liposomal system for in vivo targeted therapy with spatially and temporally precise controlled release
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DOI：
10.1016/j.biomaterials.2016.03.040
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发表时间：
2016-07-01
期刊：
影响因子：
14
通讯作者：
Sung, Hsing-Wen
中科院分区：
文献类型：
--
作者：
Chuang, Er-Yuan;Lin, Chia-Chen;Sung, Hsing-Wen
治疗药物的非特异性分布和非靶向加热通常会在癌症治疗过程中产生不良副作用，因为触发载体系统的最佳时间尚不清楚。这项工作提出了一种多功能脂质体系统，它可以在细胞内同时将治疗药物阿霉素(DOX)、热和气泡生成剂(碳酸氢铵，ABC)输送到靶向肿瘤细胞，从而产生细胞毒作用。包裹在脂质体中的金纳米胶囊有效地将近红外光照射转化为局部热，导致ABC分解并产生二氧化碳气泡，迅速触发DOX的释放。此外，杂交的粘蛋白-1适配子连接在测试脂质体的表面，然后作为识别探针来增强细胞对脂质体的摄取，并作为分子信标来通知何时内化的颗粒已经最大化，这是在全身给药后以光热方式触发药物释放的最佳时间。实验结果表明，这种联合治疗有效地以空间和时间精确的方式控制靶向药物释放，从而显著提高药物的效力，同时将不良副作用降至最低，使其成为一种有前景的癌症治疗方法。(C)2016爱思唯尔有限公司。保留所有权利。
The nonspecific distribution of therapeutic agents and nontargeted heating commonly produce undesirable side effects during cancer treatment since the optimal timing of triggering the carrier systems is unknown. This work proposes a multifunctional liposomal system that can intracellularly and simultaneously deliver the therapeutic drug doxorubicin (DOX), heat, and a bubble-generating agent (ammonium bicarbonate, ABC) into targeted tumor cells to have a cytotoxic effect. Gold nanocages that are encapsulated in liposomes effectively convert near-infrared light irradiation into localized heat, which causes the decomposition of ABC and generates CO2 bubbles, rapidly triggering the release of DOX. Additionally, a hybridized Mucin-1 aptamer is conjugated on the surface of the test liposomes, which then function as a recognition probe to enhance the uptake of those liposomes by cells, and as a molecular beacon to signal when the internalized particles have been maximized, which is the optimal time for photothermally triggering the release of the drug following the systemic administration of the liposomes. Empirical results reveal that this combined treatment effectively controls targeted drug release in a spatially and temporally precise fashion and so significantly increases the potency of the drug while minimizing unwanted side effects, making it a promising treatment for cancer. (C) 2016 Elsevier Ltd. All rights reserved.