A Synthetic Aptamer-Drug Adduct for Targeted Liver Cancer Therapy.
A Synthetic Aptamer-Drug Adduct for Targeted Liver Cancer Therapy.
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DOI：
10.1371/journal.pone.0136673
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Liu C
中科院分区：
文献类型：
--
作者：
Trinh TL;Zhu G;Xiao X;Puszyk W;Sefah K;Wu Q;Tan W;Liu C
AS 1411（以前称为AGRO 100）是一种富含鸟嘌呤的26核苷酸DNA适体，形成鸟嘌呤四链体结构。在I期和II期临床试验中，AS 1411已显示出作为癌症治疗的有希望的实用性，而不会引起重大副作用。AS 1411通过与许多肿瘤细胞膜上异常表达的核仁素结合来抑制肿瘤细胞生长。在这项研究中，我们利用一种简单的技术将广泛使用的化疗药物多柔比星（Dox）与AS 1411偶联，形成合成的药物-DNA加合物（DDA），称为AS 1411-Dox。我们通过在体外和小鼠肝癌异种移植模型中评价Dox靶向递送至Huh 7细胞，证明了AS 1411-Dox在肝细胞癌（HCC）治疗中的效用。
AS1411 (previously known as AGRO100) is a 26 nucleotide guanine-rich DNA aptamer which forms a guanine quadruplex structure. AS1411 has shown promising utility as a treatment for cancers in Phase I and Phase II clinical trials without causing major side-effects. AS1411 inhibits tumor cell growth by binding to nucleolin which is aberrantly expressed on the cell membrane of many tumors. In this study, we utilized a simple technique to conjugate a widely-used chemotherapeutic agent, doxorubicin (Dox), to AS1411 to form a synthetic Drug-DNA Adduct (DDA), termed as AS1411-Dox. We demonstrate the utility of AS1411-Dox in the treatment of hepatocellular carcinoma (HCC) by evaluating the targeted delivery of Dox to Huh7 cells in vitro and in a murine xenograft model of HCC.