Precision spherical nucleic acids for delivery of anticancer drugs,Chemical Science

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Precision spherical nucleic acids for delivery of anticancer drugs
Chemical Science ( IF 7.6 ) Pub Date : 2017-07-05 00:00:00 , DOI: 10.1039/c7sc01619k
Danny Bousmail _{1,

2,

3,

4,

5} , Lilian Amrein _{4,

5,

6,

7} , Johans J. Fakhoury _{1,

2,

3,

4,

5} , Hassan H. Fakih _{1,

2,

3,

4,

5} , John C. C. Hsu _{1,

2,

3,

4,

5} , Lawrence Panasci _{4,

5,

6,

7} , Hanadi F. Sleiman _{1,

2,

3,

4,

5}

Affiliation

We report a spherical nucleic acid (SNA) system for the delivery of BKM120, an anticancer drug for treatment of chronic lymphocytic leukemia (CLL). While promising for cancer treatment, this drug crosses the blood–brain barrier causing significant side-effects in patients. The DNA nanoparticle encapsulates BKM120 in high efficiency, and is unparalleled in its monodispersity, ease of synthesis and stability in different biological media and in serum. These DNA nanostructures demonstrate efficient uptake in human cervical cancer (HeLa) cells, and increased internalization of cargo. In vitro studies show that BKM120-loaded nanoparticles promote apoptosis in primary patient CLL lymphocytes, and act as sensitizers of other antitumor drugs, without causing non-specific inflammation. Evaluation of this drug delivery system in vivo shows long circulation times up to 24 hours, full body distribution, accumulation at tumor sites and minimal leakage through the blood–brain barrier. Our results demonstrate the great potential of these delivery vehicles as a general platform for chemotherapeutic drug delivery.

中文翻译：

用于递送抗癌药物的精密球形核酸

我们报告球形核酸（SNA）系统的BKM120，一种治疗慢性淋巴细胞性白血病（CLL）的抗癌药物的交付。尽管该药有望用于癌症治疗，但它可以穿越血脑屏障，对患者产生明显的副作用。DNA纳米颗粒高效封装BKM120，并且其单分散性，易于合成以及在不同生物介质和血清中的稳定性无与伦比。这些DNA纳米结构证明可有效摄取人类宫颈癌（HeLa）细胞，并增加了货物的内在化。体外研究表明，载有BKM120的纳米颗粒可促进原发性患者CLL淋巴细胞的凋亡，并充当其他抗肿瘤药物的敏化剂，而不会引起非特异性炎症。对体内这种药物输送系统的评估显示，其循环时间长达24小时，全身分布完整，在肿瘤部位积聚，并且通过血脑屏障的泄漏极少。我们的结果证明了这些输送工具作为化疗药物输送的通用平台的巨大潜力。

更新日期：2017-07-13

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