Acidic pH-Triggered Drug-Eluting Nanocomposites for Magnetic Resonance Imaging-Monitored Intra-arterial Drug Delivery to Hepatocellular Carcinoma.
Acidic pH-Triggered Drug-Eluting Nanocomposites for Magnetic Resonance Imaging-Monitored Intra-arterial Drug Delivery to Hepatocellular Carcinoma.
复制标题
酸性pH触发的药物洗脱纳米复合材料，用于磁共振成像对肝细胞癌的动脉内药物递送。
DOI：
10.1021/acsami.6b03505
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发表时间：
2016-05-25
影响因子：
9.5
通讯作者：
Kim DH
中科院分区：
文献类型：
--
作者：
Park W;Chen J;Cho S;Park SJ;Larson AC;Na K;Kim DH
经导管肝动脉内（IA）注射被认为是治疗肝细胞癌（HCC）的有效靶向给药技术。最近，开发了药物洗脱珠（DEB）用于经导管IA递送至HCC。然而，传统的DEB提供了相对温和的生存益处。可能难以控制药物从DEB的装载/释放以及监测向靶向肿瘤的选择性递送。肝动脉中栓塞的DEB经常诱导缺氧和低pH条件，促进癌细胞生长。在这项研究中，开发了一种酸性pH触发的药物洗脱纳米复合材料（pH-DEN），包括超顺磁性氧化铁纳米立方体和具有脂质尾的pH响应性合成肽[十八胺-p（API-L-Asp）10]，用于磁共振成像（MRI）监测索拉非尼（唯一FDA批准的肝癌全身治疗）经导管输送至HCC。合成的索拉非尼负载pH-DENs在酸性pH水平下表现出独特的pH触发药物释放行为和高度敏感的MR对比效应。在原位HCC大鼠模型中，用MRI证实了负载索拉非尼的pH-DEN的成功肝脏IA递送和分布。IA递送的载有索拉非尼的pH-DEN在啮齿动物HCC模型中引起显著的肿瘤生长抑制。这些结果表明，索拉非尼-pH-DENs平台有可能用作肝脏定向IA治疗不可切除HCC的先进工具。
Transcatheter hepatic intra-arterial (IA) injection has been considered as an effective targeted delivery technique for hepatocellular carcinoma (HCC). Recently, drug-eluting beads (DEB) were developed for transcatheter IA delivery to HCC. However, the conventional DEB has offered relatively modest survival benefits. It can be difficult to control drug loading/release from DEB and to monitor selective delivery to the targeted tumors. Embolized DEBs in hepatic arteries frequently induce hypoxic and low pH conditions, promoting cancer cell growth. In this study, an acidic pH-triggered drug-eluting nanocomposite (pH-DEN) including superparamagnetic iron oxide nanocubes and pH-responsive synthetic peptides with lipid tails [octadecylamine–p(API-L-Asp)10] was developed for magnetic resonance imaging (MRI)-monitored transcatheter delivery of sorafenib (the only FDA-approved systemic therapy for liver cancer) to HCC. The synthesized sorafenib-loaded pH-DENs exhibited distinct pH-triggered drug release behavior at acidic pH levels and highly sensitive MR contrast effects. In an orthotopic HCC rat model, successful hepatic IA delivery and distribution of sorafenib-loaded pH-DEN was confirmed with MRI. IA-delivered sorafenib-loaded pH-DENs elicited significant tumor growth inhibition in a rodent HCC model. These results indicate that the sorafenib–pH-DENs platform has the potential to be used as an advanced tool for liver-directed IA treatment of unresectable HCC.