Effect of increasing liver blood flow on nanodrug clearance by the liver for enhanced antitumor therapy
Effect of increasing liver blood flow on nanodrug clearance by the liver for enhanced antitumor therapy
复制标题
增加肝血流量对肝脏纳米药物清除的影响以增强抗肿瘤治疗
DOI：
10.1039/c8bm01371c
复制
发表时间：
2019
影响因子：
6.6
通讯作者：
Wang Changchun
中科院分区：
文献类型：
--
作者：
Li Yongjing;Wan Jiaxun;Wang Fang;Guo Jia;Wang Changchun
颗粒药物递送系统的临床应用已证明治疗效果有限，这很大程度上归因于免疫系统（尤其是肝脏中的免疫系统）消除了此类系统。受肝脏清除纳米材料机制的启发，我们引入去甲肾上腺素负载的聚丙烯酸纳米凝胶作为血管紧张素，设计了一种新型抗癌辅助递送系统。辅助系统通过增加肝脏血流量有效减少肝脏对纳米药物的摄取。超声成像直接观察到，给予所制备的负载去甲肾上腺素的聚丙烯酸纳米凝胶后，血液灌注量显着增加177.0%（即2.77倍），表明肝脏血流速度增加。由于血流速率在肝脏中纳米材料的清除中起着关键作用，因此纳米药物的清除应通过调节血流来改变。我们的体内实验结果清楚地表明，这种两步处理提高了纳米药物的效率，血浆药物浓度提高了52%，在肿瘤中药物蓄积明显，抗肿瘤效果显着。这些结果表明，涉及去甲肾上腺素负载的聚丙烯酸纳米凝胶的预处理策略可以作为减少肝脏纳米药物清除的理想途径。
The clinical applications of particulate drug delivery systems have demonstrated limited treatment outcomes, which is largely attributable to the elimination of such systems by the immune system, especially in the liver. Inspired by the mechanism of nanomaterial clearance by the liver, we designed a new anticancer auxiliary delivery system by introducing norepinephrine loaded poly(acrylic acid) nanogels as angiotonics. The auxilliary system effectively decreased the liver uptake of nanodrugs by increasing the liver blood flow rate. With administration of the as-prepared norepinephrine-loaded poly(acrylic acid) nanogels, the blood perfusion amount increased significantly by 177.0% (i.e. 2.77 times) as observed directly by ultrasonic imaging, indicating an increased blood flow rate in the liver. Since the blood flow rate plays a key role in nanomaterial clearance in the liver, nanodrug clearance should be changed by modulation of the blood flow. Our in vivo experimental results clearly showed the enhancement of nanodrug efficiency with this two-step treatment, with a 52% improvement in plasma drug concentration, obvious drug accumulation in the tumor, and significant antitumor effects. These results indicate that a pre-conditioning strategy involving norepinephrine-loaded poly(acrylic acid) nanogels can serve as an ideal route for reducing nanodrug clearance by the liver.