Bousmail Danny, Amrein Lilian, Fakhoury Johans J, Fakih Hassan H, Hsu John C C, Panasci Lawrence, Sleiman Hanadi F
Department of Chemistry , Centre for Self-Assembled Chemical Structures (CSACS) , McGill University , 801 Sherbrooke St. W. , Montreal , Canada . Email:
Department of Oncology , Jewish General Hospital , 3755 Cote Sainte-Catherine Rd. , Montreal , Canada . Email:
Chem Sci. 2017 Sep 1;8(9):6218-6229. doi: 10.1039/c7sc01619k. Epub 2017 Jul 5.
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. 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 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.
我们报告了一种用于递送BKM120的球形核酸（SNA）系统，BKM120是一种用于治疗慢性淋巴细胞白血病（CLL）的抗癌药物。尽管这种药物对癌症治疗很有前景，但它会穿过血脑屏障，给患者带来严重的副作用。DNA纳米颗粒能高效包裹BKM120，其单分散性、合成的简易性以及在不同生物介质和血清中的稳定性都是无与伦比的。这些DNA纳米结构在人宫颈癌（HeLa）细胞中表现出高效摄取，并增加了货物的内化。研究表明，负载BKM120的纳米颗粒可促进原发性CLL患者淋巴细胞凋亡，并作为其他抗肿瘤药物的增敏剂，且不会引起非特异性炎症。对这种药物递送系统的评估显示，其循环时间长达24小时，全身分布，在肿瘤部位积聚，通过血脑屏障的渗漏最小。我们的结果证明了这些递送载体作为化疗药物递送通用平台的巨大潜力。
