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首页> 外文期刊>ACS applied materials & interfaces >Acidic pH-Triggered Drug-Eluting Nanocomposites for Magnetic Resonance Imaging-Monitored Intra-arterial Drug Delivery to Hepatocellular Carcinoma
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Acidic pH-Triggered Drug-Eluting Nanocomposites for Magnetic Resonance Imaging-Monitored Intra-arterial Drug Delivery to Hepatocellular Carcinoma

机译：酸性pH触发的药物洗脱纳米复合材料，用于磁共振成像监测动脉内药物向肝细胞癌的递送。

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摘要

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.
机译：经导管肝动脉内（IA）注射已被认为是肝细胞癌（HCC）的有效靶向递送技术。近来，开发了药物洗脱珠（DEB），用于经导管IA递送至HCC。但是，传统的DEB提供了相对适中的生存优势。可能难以控制药物从DEB的负载/释放以及监测对靶向肿瘤的选择性递送。肝动脉中栓塞的DEB经常诱发缺氧和低pH条件，从而促进癌细胞的生长。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物（pH-DEN），该复合物包括超顺磁性氧化铁纳米立方体和具有脂质尾巴的pH敏感合成肽[十八烷基胺p（API-L-Asp）（10）]。成像（MRI）监测的索拉非尼（经FDA批准的唯一用于肝癌的全身疗法）经导管输送至肝癌。合成的索拉非尼负载的pH-DEN在酸性pH值下表现出独特的pH触发药物释放行为，并具有高度敏感的MR对比效应。在原位肝癌大鼠模型中，MRI证实了索拉非尼负载的pH-DEN的肝IA传递成功和分布。在啮齿动物HCC模型中，IA递送的索拉非尼负载的pH-DENs引起显着的肿瘤生长抑制。这些结果表明，索拉非尼的pH-DENs平台有可能被用作肝定向IA治疗不可切除HCC的先进工具。

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