MRI-detectable polymeric micelles incorporating platinum anticancer drugs enhance survival in an advanced hepatocellular carcinoma model.
MRI-detectable polymeric micelles incorporating platinum anticancer drugs enhance survival in an advanced hepatocellular carcinoma model.
复制标题
DOI：
10.2147/ijn.s81339
复制
发表时间：
2015
影响因子：
8
通讯作者：
Tani T
中科院分区：
文献类型：
--
作者：
Vinh NQ;Naka S;Cabral H;Murayama H;Kaida S;Kataoka K;Morikawa S;Tani T
肝细胞癌（HCC）是最难治性和致死性的癌症之一；大多数病例在晚期诊断为潜在的肝功能障碍，并且经常对常规化疗和放疗产生耐药性。肿瘤靶向系统的发展可能会改善治疗效果。纳米医学平台对提高化疗效率特别感兴趣，它们包括聚合物胶束，可以将多种药物靶向实体肿瘤，包括成像和治疗剂。这允许并发诊断、靶向策略验证和疗效评估。我们使用含有t1加权磁共振成像造影剂钆-二乙烯三胺五乙酸（Gd-DTPA）和抗癌药物奥沙利铂（（1,2-二氨基环己烷）铂（II） （DACHPt））母体复合物的聚合物胶束，在原位大鼠肝细胞癌模型中同时成像和治疗。将负载Gd-DTPA/ dachpt的胶束注入肝动脉，评估其磁共振成像性能、抗肝癌活性及药物不良反应。单次给药后，胶束实现了强而特异性的肿瘤对比增强，诱导了高水平的肿瘤凋亡，并显著抑制了肿瘤的大小和生长。此外，与奥沙利铂或生理盐水对照组相比，胶束不会引起严重的不良反应，并显著改善了生存结果。我们的研究结果表明，Gd-DTPA/ dachpt负载胶束是一种有效诊断和治疗晚期HCC的有希望的方法。
Hepatocellular carcinoma (HCC) is one of the most intractable and lethal cancers; most cases are diagnosed at advanced stages with underlying liver dysfunction and are frequently resistant to conventional chemotherapy and radiotherapy. The development of tumor-targeting systems may improve treatment outcomes. Nanomedicine platforms are of particular interest for enhancing chemotherapeutic efficiency, and they include polymeric micelles, which enable targeting of multiple drugs to solid tumors, including imaging and therapeutic agents. This allows concurrent diagnosis, targeting strategy validation, and efficacy assessment. We used polymeric micelles containing the T1-weighted magnetic resonance imaging contrast agent gadolinium-diethylenetriaminpentaacetic acid (Gd-DTPA) and the parent complex of the anticancer drug oxaliplatin [(1,2-diaminocyclohexane)platinum(II) (DACHPt)] for simultaneous imaging and therapy in an orthotopic rat model of HCC. The Gd-DTPA/DACHPt-loaded micelles were injected into the hepatic artery, and magnetic resonance imaging performance and antitumor activity against HCC, as well as adverse drug reactions were assessed. After a single administration, the micelles achieved strong and specific tumor contrast enhancement, induced high levels of tumor apoptosis, and significantly suppressed tumor size and growth. Moreover, the micelles did not induce severe adverse reactions and significantly improved survival outcomes in comparison to oxaliplatin or saline controls. Our results suggest that Gd-DTPA/DACHPt-loaded micelles are a promising approach for effective diagnosis and treatment of advanced HCC.