AS1411-conjugated gold nanospheres and their potential for breast cancer therapy.
AS1411-conjugated gold nanospheres and their potential for breast cancer therapy.
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DOI：
10.18632/oncotarget.4207
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发表时间：
2015-09-08
期刊：
影响因子：
--
通讯作者：
Bates PJ
中科院分区：
文献类型：
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作者：
Malik MT;O'Toole MG;Casson LK;Thomas SD;Bardi GT;Reyes-Reyes EM;Ng CK;Kang KA;Bates PJ
AS 1411是一种形成四链体的DNA寡核苷酸，作为靶向核仁素（一种存在于癌细胞表面的蛋白质）的适体发挥作用。AS 1411的临床试验表明，它具有良好的耐受性和治疗活性，但可能需要改善药理学和效价才能获得最佳疗效。在这份报告中，我们描述了如何共轭AS 1411 5 nm金纳米球影响其在体外和体内的活动。我们发现AS 1411连接的金纳米球（AS 1411-GNS）在水溶液和含血清溶液中稳定。与未缀合的AS 1411或与对照寡核苷酸连接的GNS相比，AS 1411-GNS具有上级细胞摄取和显著增加的抗增殖/细胞毒性作用。与AS 1411相似，与非恶性细胞相比，AS 1411-GNS显示出对癌细胞的选择性。在乳腺癌小鼠模型中，全身给予AS 1411-GNS可完全抑制肿瘤生长，无毒性迹象。这些结果表明AS 1411-GNS是临床翻译的有前途的候选者。
AS1411 is a quadruplex-forming DNA oligonucleotide that functions as an aptamer to target nucleolin, a protein present on the surface of cancer cells. Clinical trials of AS1411 have indicated it is well tolerated with evidence of therapeutic activity, but improved pharmacology and potency may be required for optimal efficacy. In this report, we describe how conjugating AS1411 to 5 nm gold nanospheres influences its activities in vitro and in vivo. We find that the AS1411-linked gold nanospheres (AS1411-GNS) are stable in aqueous and serum-containing solutions. Compared to unconjugated AS1411 or GNS linked to control oligonucleotides, AS1411-GNS have superior cellular uptake and markedly increased antiproliferative/cytotoxic effects. Similar to AS1411, AS1411-GNS show selectivity for cancer cells compared to non-malignant cells. In a mouse model of breast cancer, systemic administration of AS1411-GNS could completely inhibit tumor growth with no signs of toxicity. These results suggest AS1411-GNS are promising candidates for clinical translation.