Department of Mechanical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University, Evanston, IL, USA.
Division of Oral Biology and Medicine, Division of Advanced Prosthodontics, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA School of Dentistry, California NanoSystems Institute, and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.
Nanomedicine. 2014 Feb;10(2):359-69. doi: 10.1016/j.nano.2013.07.014. Epub 2013 Aug 3.
Nanodiamonds (NDs) are promising candidates in nanomedicine, demonstrating significant potential as gene/drug delivery platforms for cancer therapy. We have synthesized ND vectors capable of chemotherapeutic loading and delivery with applications towards chemoresistant leukemia. The loading of Daunorubicin (DNR) onto NDs was optimized by adjusting reaction parameters such as acidity and concentration. The resulting conjugate, a novel therapeutic payload for NDs, was characterized extensively for size, surface charge, and loading efficiency. A K562 human myelogenous leukemia cell line, with multidrug resistance conferred by incremental DNR exposure, was used to demonstrate the efficacy enhancement resulting from ND-based delivery. While resistant K562 cells were able to overcome treatment from DNR alone, as compared with non-resistant K562 cells, NDs were able to improve DNR delivery into resistant K562 cells. By overcoming efflux mechanisms present in this resistant leukemia line, ND-enabled therapeutics have demonstrated the potential to improve cancer treatment efficacy, especially towards resistant strains.
The authors of this study demonstrate superior treatment properties of resistant leukemia cell lines by utilizing nanodiamond vectors loaded with daunorubicin, paving the way to clinical studies in the hopefully not too distant future.
纳米金刚石(NDs)在纳米医学中具有很大的应用潜力,在癌症治疗的基因/药物传递平台方面显示出了巨大的潜力。我们已经合成了能够进行化疗药物负载和传递的 ND 载体,并将其应用于耐化疗白血病。通过调整酸度和浓度等反应参数来优化道诺霉素(DNR)在 ND 上的负载。所得的结合物是 ND 的新型治疗有效载荷,对其大小、表面电荷和负载效率进行了广泛的表征。使用具有多药耐药性的人髓性白血病细胞系 K562(通过递增的 DNR 暴露赋予)来证明基于 ND 的递送所带来的疗效增强。虽然耐药 K562 细胞能够克服单独使用 DNR 的治疗,但与非耐药 K562 细胞相比,ND 能够改善 DNR 向耐药 K562 细胞的传递。通过克服这种耐药白血病系中存在的外排机制,ND 增强的治疗药物具有提高癌症治疗效果的潜力,特别是针对耐药株。
本研究的作者通过利用负载道诺霉素的纳米金刚石载体,展示了耐药白血病细胞系的优越治疗特性,为在不久的将来开展临床研究铺平了道路。